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Gram‑Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract

Kline, Kimberly A.; Lewis, Amanda L.

2016

Kline, K. A., & Lewis, A. L. (2016). Gram‑Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract. Microbiology Spectrum, 4(2). https://hdl.handle.net/10356/85576 https://doi.org/10.1128/microbiolspec.UTI‑0012‑2012

© 2016 American Society for Microbiology (ASM). This is the author created version of a work that has been peer reviewed and accepted for publication by Microbiology Spectrum, American Society for Microbiology (ASM). It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1128/microbiolspec.UTI‑0012‑2012].

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g e w 38 obial UTI obial gizes with UPEC in the murine urinary tract, such tract, urinary murine the in UPEC with gizes esti r r v mirabilis n ust cathete ailable in PMC 2016 June 01.

occur in the urine of ind urine the occur in . v b - a P syne ys by UPEC [ by UPEC ys ylococcus , we will will , we ymic e r l h eral i icantly more often when the t the when often more icantly v f e also also erity of sequelae. of erity , immune compromised, and those with indwelling cathet indwelling with those and compromised, , immune v y Stap anisms anisms e ace of ro ace or po or f g f r the urinary tract by UPEC and UPEC and by tract urinary the yticus, Enterococcus gy between these t these gy between h r e o v as inoculated alone [ alone as inoculated e rise to greater CFU for both both for CFU greater rise to e ]. Similar studies in mice sh mice in studies Similar ]. i mirabilis

v w ilms that arise in catheterized ind catheterized that arise in ilms . Author manuscript; at ays in in ays a f

37 . P g g , and diabetes. Polymicrobial UTI is less common among young s young among less common is UTI Polymicrobial , and diabetes. , w ilms are often polymicrobial in nature [ nature in polymicrobial are often ilms A sequence analysis of bacterial bio bacterial of analysis A sequence saprop e y f

]. ]. n c N and UPEC in a murine UTI model h UTI model murine a in and UPEC - 36 anisms commonly co commonly anisms e bio 33 , g ]. Microscopic and microbial culture culture microbial and Microscopic ]. v r yelonephritis signi yelonephritis infection resulted in a more rapid d rapid a more in resulted infection i p - 20 incidence of urinary stones (urolithiasis) and bacteremia in a murine model of of in model a murine bacteremia and (urolithiasis) stones of urinary incidence 40 xt section of this chapte xt section omen. Since the highly polymicrobial microbiota of the GI and reproduct GI and the of microbiota polymicrobial highly the Since omen. co UTI bio e infection infection

- e Gram e posit w A - ylococcus v i e presence of multiple recognized uropathogens in midstream urine at titers >100,000 urine titers at midstream in uropathogens recognized of multiple presence h , malignan Microbiol Spectr

ed microbial inoculation into the urinary tracts of model o of model tracts urinary into the inoculation ed microbial v y these o y these i V x o species [ o species fects in ascending UTI, the nature of the ofmi the nature UTI, the ascending fects in h f atheters [ atheters aecalis w independent D independent that C e or s spectrum the influence n In the Gram isolated frequently most the to response and host Stap ascending UTI compared to monomicrobial infection [ infection to monomicrobial UTI compared ascending w c f species when each Streptococcus high titer persistent to susceptibility host and alter host immunity modulate GBS can kidn and bladder of the infection cont the in infection to UPEC prone particularly age to compared of GBS presence the in infection UPEC titer higher [ controls mi of inoculation transurethral ascending syne a suggesting infection, species to single compared together t that co of complementar use The infection. species single either path metabolism syne promote and thus posit increased continue to be useful in the search for antimicrobial agents aimed prat aimed agents antimicrobial for search the in useful be to continue Gram The occur infections Polymicrobial UTI. of etiology polymicrobial consistent with a is CFU/ml elderl the often among most HI act truly and since UTI, to leading source inoculation be a major to are thought s arise, UTI do polymicrobial persistent infection in the in infection persistent the e test to used been recently has model murine wis e Epidemiology and animal models models animal and Epidemiology Kline and L

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79 80 yticus atty acids such as linoleic acid are acid are as linoleic acids such atty w and in GspB yticus to the to , serine that occur in the urine is the urine in that occur serine

, f ]. The presence of urease of presence The ]. 82 h h S. - strain vitro saprop

aureus 24 79 23 ]. ].

ibrinogen, and human bladder epithelial epithelial bladder human and ibrinogen, ys, for inflammation in the bladde the in for inflammation ys, in S. f e S. 92 ents binding to urothelial cells, perhaps via via perhaps cells, urothelial to binding ents alently attach a subset of secreted proteins proteins secreted of a subset attach alently ]. aureus adherence adherence saprop

saprop v

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e strains, is i strains, o h 78 xposure, in biological niches such as the the as such niches in biological xposure, S.

S. S. e associated sortase substrates compared to other other to substrates compared sortase associated

e accessory secretion secretion e accessory UafA, UafB, SdrI, and Sss SdrI, UafA, UafB, with bacterial sur bacterial with

v : ]. Uro ]. i all gulates the virulence determinant Ssp in the presence presence the Ssp in determinant virulence the gulates encoded UafB, found in ~5% of strains strains of in ~5% found encoded UafB, - e yticus saprop y infections [ y infections w ibronectin, ibronectin,

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yticus [ plasmids ferent ylococcus epidermidis e bacteria c e bacteria f ] h h v e cell i di 7108 [ 93 v saprop

i

o , the mechanism by which Ssp contri Ssp which by mechanism , the yticus ]. Plasmid ]. r mediates resistance to complement resistance mediates Stap w S. aspartate h e

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saprop all associated proteins, proteins, associated all irst sequenced sequenced irst h

f serine deaminase mutants are outcompeted by the isogenic wild type type wild isogenic by the outcompeted are mutants deaminase serine Author manuscript; - w

ys in a murine model of UTI [ UTI of model a murine ys in S. ]. H ]. - . enting interactions of adhesin(s) with the cells [ cells with the of adhesin(s) interactions enting to tolerate high concentrations of D of high concentrations to tolerate ed among among ed e ery f v important prior to urethral urethral to prior important aureus saprop serine deaminase, found in in found deaminase, serine v

e v 76 - undant [ undant has been associated associated has been containing proteins predicted to be cell be cell to predicted proteins containing – - S. saprop b

74 S. yticus oding genetic locus in the sequenced strain is found on an SCC genetic element element genetic SCC on an found is strain sequenced in the locus genetic oding , attached sur attached associated serine associated h - understood. rich glycoprotein that binds binds that glycoprotein rich - xamined to date [ date to xamined - yticus - 24 e rich platelet binding proteins SraP in SraP proteins binding platelet rich e pathogens, these accessory Sec systems are associated with virulence [ virulence with are associated Sec systems accessory these pathogens, e h all ut does not promote bladder colonization in a murine UTI model [ UTI model murine a in colonization bladder promote notut does icient colonization of the bladder and kidn and bladder of the colonization icient all - ylococcus v f serine, and D and serine, ylococci. The ylococci. b i w f - h w Microbiol Spectr h well e been described in in described been e ] (Figure 1C). 1C). (Figure ] saprop v

a ut does not play a role in uropathogenesis in a murine model. Instead, SssF has been has SssF Instead, model. a murine in uropathogenesis a role in play not ut does 91 S. by D conferred [ of D kidn the strain in whose enc the to is similar arrangement genetic and whose of capsule [ neutrophils by human killing pr and masking Stap conser is highly b be to postulated polyunsaturated where area or periurethral perineum a particularly to cell In addition for e UTI [ of a rat model in spleen to the dissemination saprop strains strains a serine cells serine [ system secretion SecA2 accessory on an rely which putat for a gene contains that also locus posit cell associated is binds collagen, that strains, kidn persistent UTI and acute role in adhes the with homology structural Cell Cell Gram in enzymes Sortase signals, sorting or motifs, recognition sortase bearing signal sorting h possess strains stap [ UafA on its chromosome, substrate sortase Sss UafB and as well unsequenced cells epithelial bladder adhesion to that mediates model [ model not wis e Kline and L

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vities alone or in cooperation in cooperation or alone vities

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el el ABC S. k ]. In the mouse transurethral model model transurethral mouse the In ]. vity vity 115 106 inflammatory inflammatory i e been identi been e associated infections associated with with associated associated infections or -

- , v ealed the presence of 3 putat presence the ealed wth conditions promote bio promote wth conditions resistant and resistant a yticus PSMs are recruit, act recruit, - v o 116 bacteria into the murine murine into the bacteria h 50 h e o nic

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are usually encoded within the core genomes, genomes, core the within encoded are usually h saprop - v

, n that do not appear to be associated with MGEs MGEs with associated be to appear do not that isolates [ isolates

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ilm UTI in humans is not mar not is UTI humans in e antibacterial act antibacterial e ylococcal pro ylococcal core genomic PSM has been found that is instead is instead found that been PSM has genomic core

f e catheterized and pr and catheterized v - acquired infections where th where infections acquired polysaccharide is acting. polysaccharide aureus PSM ]. h y are able to to able y are in their peptide form, whereas PSMs that assemble assemble that whereas PSMs form, in their peptide - v

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k v S. able to colonize the bladder at a similar frequen similar a at bladder the colonize able to a S. yticus 106 S. ailable in PMC 2016 June 01. yticus h v is is a member of the human skin microbiota microbiota skin human of the is a member a h

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ation and are summarized in a recent r recent a in summarized are and ation e g S. S. xperimentally determined. xperimentally pathogenesis, inoculation of 10 of inoculation pathogenesis, aureus , ]. Ma ]. aureus xtracellular xtracellular e Author manuscript; virulence virulence

r ]. One One ]. e

e 80% identity to PSMβ1/2 80% identity . esti v – S. 99 saprop i S. e yuria, hematuria, and flank pain [ pain flank and hematuria, yuria,

v – ylococcal UTI ylococcal k p n at 105 S. e UTI and is characterized by symptoms such l as symptoms by is characterized UTI and e ] and are associated with 2.5% of C 2.5% with associated and are ] li h g – yticus unpublished). Whether Whether unpublished). are a lead cause of hospital are cause a lead ylococcal UTI ylococcal 96 - v

e e i e h i e been identi , aureus transporter that imports nic that imports transporter h v

icantly delayed kinetics, compared to to compared kinetics, delayed icantly v - i at f also also encodes an act 114 103 a S. g e UTI more often occurs in urinary often occurs UTI more utions of capsule of other uropathogens, such as UPEC [ UPEC as such uropathogens, other of capsule of utions n

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v n yticus stap yticus resistant [ resistant of cathete absence with signi to response The immune Gram inflammation, of S. Opp5a) h third ABC i no other n Coagulase in bio especially pathogen, opportunistic important d medical indwelling of act area epidermidis sequenced genome of genome sequenced PSMβ1 to homologous 55 with peptides (K.A. Kline, be to UTI remains to In contrast aureus of The majority d subsequent with associated Phenol soluble modulins ( modulins soluble Phenol in characterized in immune crucial and are [ neutrophils [ niche a within microbes other kill can that peptides host antimicrobial with bio mediate PSMs also into amyloid [ stability SCC the with associated [ virulence and resistance methicillin human multiple including contri this UTI of stages at which to determine h op

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f S. h hemolytic

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], others report that that report others ], w - 126 ed, with ~100 ed, v , aecium saprop 125 kidn

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121 E. 118 w the host handles host w the E. 124 are also at increased risk for UTI [ for risk increased at also are o unit protein of the mitochondrial compl mitochondrial of the protein unit

b , all of which pea ofwhich , all 19 mice produce l produce 19 mice yelonephritis after after intr yelonephritis r - p e anaerobes are γ are e anaerobes , a role for the mitochondrial respiratory chain chain respiratory mitochondrial , a for the role y titers obser y titers PMC 2016 June 01. omen [ omen y v

e i diabetics [ diabetics viduals viduals - i ytokines and signi and ytokines w c bladde ococci alent among among alent e that typically occur as occur that typically bacteria acid e lactic e for intracellular killing of killing intracellular e for innate inflammatory immune response to to response immune inflammatory innate r v v out of a su of out i etic etic i ev - induced (alloxan) diabetic rats and non rats and diabetic (alloxan) induced w outnumbers w outnumbers acultat ed in UTI described to date are also bio also date are to described UTI in ed ailable in - ], whereas whereas ], f ilms on abiotic sur on abiotic ilms o v v f a ]. Recentl ]. diab posit ol animal studies. In a chemically studies. In animal - ]. The The ]. - 127 v 24 fold more CFU from the from CFU more fold n y Ente y - 61 actor for prostatitis, for which enterococci are responsible for responsible are enterococci for which prostatitis, for actor UTI n , f due to of UTIs The incidence ].

b associated UTIs and are the third leading cause of hospital of cause leading third the are and UTIs associated ]. Diabetic ind Diabetic ]. - inflammatory inflammatory r innate immune response to response immune innate 49 - UTI[ elops bio elops

130

v irst mechanistic study of h study irst mechanistic 119 , act that do not form [ spores form do not that act actors i actors e f , f f y compared to the the to y compared aecalis e f

129 ery of 100 of ery yticus 115 E. are more often associated with UTI among diabetics and cause 13% of 13% and cause diabetics UTI among with often associated more are h Author manuscript;

,

ov . diabetic mice [ mice diabetic resistant enterococcal strains presents a signi presents strains enterococcal resistant 9.9, sodium chloride concentrations up to 6.5%, bile salts up to 40%, and and up to 40%, salts bile up to 6.5%, concentrations chloride 9.9, sodium - es as a nidus for the higher incidence of bacteremia in this population [ in this population of bacteremia incidence higher for the nidus a es as - 13 – are responsible for a minority of community of minority for a are responsible v similar in chemically similar ytokines and are defect and are ytokines

e been reflected in in reflected e been UTI reflected the higher kidn higher the UTI reflected in a murine model may reflect the propensity of this o this of propensity the reflect may model in a murine c 10 from ranges temperature including conditions vironmental spp.

v n as ) is prone to spontaneous urinary tract infection by infection tract urinary spontaneous to prone ) is a saprop infection, macrophages from GRIM from macrophages infection, drug

ococcal UTI ococcal w - omen compared to non to compared omen r

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f v i yelonephritis in humans [ in humans yelonephritis ancomycin resistance increasingly pr increasingly resistance ancomycin 128 E. [ [ of cases up to 10% ov to multiple v d to and adheres readily virulence enterococcal and of cathete 30% 15 to cause [ UTIs acquired 121 123 diabetic Enterococcus in non 4.9% to compared diabetics ASB in h in humans to susceptible were more mice diabetic diabetes, of murine model non to compared inflammatory inflammatory this reflects report This infection. of Gram a genus are Enterococci These chains. or in short diplococci d 4.6 from ranges the despite desiccation saprop p saprop pro numerous of induction in to the bladder recruitment macrophage Enhanced infection. of stages in the implicated has been knock a heterogeneous strain carrying I ( to response resulted in the rec in the resulted [ post infection 2 weeks as long as for and infection post hours ract In T

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e immunity and e immunity

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mutant is attenuated in is attenuated mutant i actors i actors w , 152 AS) motif in the in AS) motif f dia o o , ilm formation, and and formation, ilm - vitro D f and MI and v

i ebp ylated lipotechoic acid acid lipotechoic ylated -

v in y colonization during y colonization n ]. H ].

151 onization in a mouse model, model, a mouse in onization aecalis e , all proteins in addition to the the to addition in proteins all f actors function in a similar a similar in function actors in

f ala

gulatory system and, system gulatory w virulence in animal models models animal in virulence - 149 27 e ation substance [ substance ation E. o , g ace protein that is enriched among among is enriched that protein ace UTI, bio UTI, and aecium e f Streptococcus

mutans are signi are mutans f 30 A ibronectin binding protein EfbA [ EfbA protein binding ibronectin

) relies on a pilus on a ) relies e bacteria, biogenesis of the of the biogenesis e bacteria, f A domain v E. i W vitro ]. Furthermore, SrtA and the Ebp are are Ebp the SrtA and Furthermore, ].

amily transcription amily ahrC Ebp UTI [ UTI ute to ur ute to gA of gA terminus of EbpA, the li the of EbpA, terminus f G), and D G), and ution to infection in the absence of foreign offoreign absence in the infection to ution r - in ilm formation formation ilm b A ut not SrtA, are important for ascending important are SrtA, notut f b posit

148 ]. An ]. emporal analysis of analysis emporal b - component r component gR , DA ]. T actors monoglucosyl actors - r f ) proteins and human platelets platelets human and ) proteins o

]. The V The ]. ]. ]. 149 dependent C dependent w 144 137 - ge ~200kD sur ~200kD ge , r vitro, and and vitro, 155 147

during C [

– SrtA is important for the early attachment stage of attachment the early for is important SrtA ECM

all, including aggr including all,

in o utable to multiple cell cell to multiple utable (MI site adhesion dependent o aecalis 136 ]. The A The ]. ut its contri ut its - w f v [ ailable in PMC 2016 June 01. b v

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i b v 144 pathogen interaction in the urinary tract [ tract urinary in the interaction pathogen ]. Esp promotes bladder col bladder promotes Esp ]. v a

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, E. 140 associated pilus ( pilus associated - in in 77 vitro 135

e domains, sharing sequence similarity with Rib and C alpha C alpha with and Rib similarity sequence sharing e domains, ]. Thus, it appears clear that clear appears it Thus, ]. – wed that v ylglycerol (DGlc ylglycerol ilm SrtC and the Ebp, Ebp, SrtC the and the cell cell the i in o f c

153 132 sh ace proteins that contri that proteins ace f A) domain within the N within the domain A) SrtC) for pilus polymerization and the house the and polymerization pilus SrtC) for dia

- assembled pili in Gram in pili assembled ilm formation ilm W - formation and infection in the absence of abiotic d of abiotic the absence in and infection formation , it is unclear whether these virulence virulence these whether unclear , it is f

r sur

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v proteinacious proteinacious gulated by the GrvRS t the by gulated asion [ asion ace protein Esp is a la is Esp protein ace ilm ilm - e xtracellular matrix ( matrix xtracellular Author manuscript; e f mutants are attenuated for bio for attenuated are mutants f in

E. ilm formation formation ilm

e . predicted metal ion metal predicted ev aecalis, w f all anchoring [ anchoring all f o

sur w aecalis

wth on catheters as well as for bladder and kidn bladder and for as well as catheters wth on , a ilm formation formation ilm f dder colonization colonization dder E.

o f y gvrR ]. Non ]. actor A (V A actor f , E. as found to be essential for Ebp essential be to found as ution of SrtA may be attri may of SrtA ution y G), diglucosyl G), b w 141 ]. Ace is r Ace ]. endocarditis and bio and endocarditis aecalis ilm gr ilm

the absence of catheter in an outbred mouse model [ model mouse an outbred in of catheter absence the f

f DA ) for cell cell for ) 139 E. Microbiol Spectr ilm formation during infection, infection, formation during ilm ilm formation ilm [ Ebp and the is SrtC formation, as ilm ]. Recentl ]. , A) appear to limit UTI virulence because mutations in synthetic genes for each of these of these for each genes synthetic in mutations because UTI virulence limit to A) appear UTI [ UTI f f f vices may be species dependent. be species vices may illebrand illebrand T A e xpression interferes with the host the with interferes xpression SrtA L aecalis the ascending UTI model [ UTI model the ascending bio d bind can pili Ebp 154 W the Ebp, bla associated R pilin tip as the as well GBS, of PilA containing f C in (Sortase ( bio bio bio for important to proteins multiple attaches the contri In contrast, pilus. UTI in [ mice inbred UTI in for ascending required accordingl [ UTI ascending of model murine bio for early important for bio C (MGlc ( cells urothelial of colonization increase products e tosortase other Similar The fecal to compared isolates endocarditis and bloodstream enterococcal repetit multiple of composed protect which confer B streptococci, in group determinants virulence immune mediate bio as as well Additional the enterococcal Ace and adhesin collagen the include 138 determinants. H determinants. bio during manner UTI virulence facto virulence UTI wis e E. faecalis faecalis E. Kline and L

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169 e , e rise to dysuria, urinary dysuria, rise to e ]. More ]. suggesting lack of adherence of adherence lack suggesting v

166 i 24 y tropism is a common theme theme is a common y tropism – aecium ]. ], ]. Despite being commonly commonly being Despite ]. 15 f e binding oligimerization domain oligimerization binding

- y infection. Aggr y infection. , Gram 85 26 transiently transfected 293 cells transfected transiently e oiding, and the same same the and oiding, aecalis oxidation, not only promote promote only not oxidation, r ut also during ascending UTI ascending during ut also E. - 162 f v 172 e

b ]. A number of A number ]. , , wer urinary tract symptoms (LUTS) symptoms tract urinary wer – v r o e E. e receptor 2 receptor e e k v ]. Kidn ]. pathogenic o pathogenic w y 162 139 e - 170 li [ o h

- , w eolar and intestinal intestinal and eolar mediated immune in immune mediated 159 o - v [ A domain of the PilA tip pilin of GBS is GBS is of pilin tip PilA of the A domain 15

W erse protein protein erse ]. H ]. v aecalis f yuria. H yuria. e vitro

either in TLR2 either in p aecalis

macrophages may be important for the ability of ability for the important be may macrophages 168 f E.

in xperimental peritonitis [ peritonitis xperimental , edema [ edema e

E. xplanation w xplanation EbpA mediates binding to host host to binding EbpA mediates ]. The V The ]. 26

e al within human neutrophils [ neutrophils human within al ailable in PMC 2016 June 01. icient to clear the kidn the clear to icient aecalis v f iv f f a ] and it has been proposed that glycosaminoglycans on glycosaminoglycans that proposed been it has and ] 157 with urine storage and and storage urine with

e stress responses [ responses e stress , UTI is rarely symptomatic [ symptomatic rarely is UTI ertheless, urothelial cells containing intracellular intracellular containing cells urothelial ertheless, al within within al peptidoglycan fragments [ fragments peptidoglycan v E.

i v

A aecalis surv iv 161 e can colonize and persist in the kidn the in persist and can colonize f

al within macrophages, including including within macrophages, al inflammatory signaling cascades can also be induced via induced be also can cascades signaling inflammatory [ of mono primarily consisted post infection, days 2 ys at

156 - e iv as insu as delineated. In mice, toll In mice, delineated. E. . N r - w mediated signaling, and these are thought to be important for important be thought to are these and signaling, mediated aecalis - f lactis

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o Author manuscript; UTI is accompanied by accompanied is UTI i iv

]. . ococcal UTI ococcal ed in the urine of patients displaying l displaying patients of urine in the ed A r v infected kidn infected AS motif of AS motif ed in TLR ed in ade human urothelial cells cells urothelial human ade in the bladde in the 158 D v

v ace, pr ace, n f ol Lactococcus UTI and where surv UTIwhere and

v n ) protein and protein ) UTI [ UTI ogether these studies present a picture in which macrophages are a are macrophages in which picture a present studies these ogether or in the murine urinary tract [ tract urinary murine or in the , urothelial damage, and bladder and bladder damage, , urothelial and and A y aecalis T ed in the the in ed ed in the host response to host response in the ed

e longer within macrophages compared to non to compared macrophages within e longer al within act within al The MI The f c

e into macrophages, pro macrophages, into e v

v . v ]. ]. k iv i Microbiol Spectr aecalis e been implicated in surv implicated been e e been obser been e E. ol f Nod2 vitro v v

gen v a a r xtracellular matrix proteins [ proteins matrix xtracellular 167 n signaling neutrophil recruitment during during recruitment neutrophil signaling upta nucleotide macrophage the intracellular between interaction 2 ( C UTI, ascending to In contrast g can infection, of bacterial absence in the alone, catherization u C asymptomatic, surv [ E. niche. this within persist to enterococci to leading cascades signaling The host well not yet is tract urinary to Gram responses innate immune initiate to lipopeptides recognizes i in protein adaptor intracellular the and TLR2 both requires macrophages peritoneal murine i MyD88 strains can i can strains posit Gram among obser and and neutrophils, cells promotes substance surv DH5α sur the macrophage h oxidat and Ace, polysaccharide, r to predicted B, A and reductases sulfoxide vitro coats the and subsequently implantation catheter to response in bladder the in released sur catheter with C model, In a murine [ inflammation of apparent absence in the the bladder from by h associated and issues pain as such e al human to adhesion for bacterial important also wis e une responses to ente une responses m Im Kline and L

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e v f - wn that a subset of strains were were of strains subset wn that a xtran Sulphate Sodium salt (DSS) salt Sodium Sulphate xtran o strains isolated from the from strains isolated UTI, mar

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r gnant, diabetic, and and diabetic, gnant, a wnr and macrophage inflammatory protein inflammatory macrophage and e

e aecalis o 180 f y as 39% of nursing home residents residents home nursing of y as 39% ]. Infection of catheterized mice mice of catheterized Infection ].

e o although the presence of presence the although ilm on cathete the ilm n

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- D a in responses ytokine eral studies of eral studies can 179 ]. In addition, there is a is there In addition, ].

c v y G y – E. e y human in y human e [ e bacilli b h v i 174 UTI isolates and can d can and UTI isolates forming coccus that is a common asymptomatic inhabitant of the of inhabitant asymptomatic common is a that coccus forming

[ UTI model where implantation of a foreign body (catheter) alone alone (catheter) body of a foreign implantation where model UTI 177 - viduals, as well as those with prewith those well as as viduals, ving catheter alone [ alone ving catheter

at otherwise kn otherwise i i measured by leu measured

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1 ]. Despite high high Despite ]. UTI associated with Gram with UTI associated a 182 iv despite bacterial loads in the bladder bladder the loads in bacterial despite

histopathology including edema, urothelium damage, and proinflammatory proinflammatory and damage, urothelium edema, including histopathology w anw i ,

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e 192 201 w – ating whether l whether ating fold increased fold increased e rectal colonization at 35 at colonization rectal gnant gnant 187 - ], with approximately 160,000 cases 160,000 cases approximately with ], g - v e actor for maternal for maternal actor i wborns and can be acquired by the acquired be can and wborns 189

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aginal 187 ], it has been estimated that up to 7% of of 7% that up to estimated been it has ], - b v e an apparent focal origin such as cellulitis, cellulitis, as such origin focal an apparent e omen underwent urine culture [ culture urine underwent omen v e a 20 e a a w ]. In about 30% of cases, systemic infections infections systemic cases, of 30% In about ]. 180 v a omen who test n who test omen erse maternal or neonatal outcomes. One study One study outcomes. neonatal or maternal erse v w 186 , h inding, inding, 2% [ 2% viduals; 14% viduals; , y f i – er viduals with GBS urosepsis include diabetes mellitus, mellitus, diabetes include urosepsis GBS with viduals i v 185 i concentration of GBS detected in in detected of GBS concentration ailable in PMC 2016 June 01.

v w titer GBS bacteriuria were at higher risk of GBS of GBS risk at higher were bacteriuria GBS w titer y a o n a ylaxis for culture ylaxis e for GBS in urine GBS e for h v i y GBS colonies in urine cultures from all all from cultures urine in colonies y GBS

imated 1 at imated n icant titers of GBS in urine [ urine in GBS of titers icant f y disease, recurrent urinary tract infections, obstruct infections, urinary tract recurrent y disease, ].” e tract, GBS is often found to colonize the urinary tracts of tracts urinary the colonize to found is often GBS e tract, gnant adults do not h do not adults gnant e v ersal screening of GBS of GBS screening ersal e i v wth in urine of other pathogens at concentrations < 10 < concentrations at pathogens other of urine wth in irm or refute this this refute or irm i omen without detectable GBS in urine [ urine GBS in detectable without omen ]. The 2002 recommendations from the CDC stated that clinical that clinical the CDC stated from recommendations 2002 The ]. 199 f o omen with l with omen whether urine samples are from pr are from samples urine whether w e signi e

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v 198 w y Author manuscript; a

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e age [ e age w gnant adults, the incidence of systemic GBS infections is estimated at estimated is GBS infections systemic of incidence the adults, gnant v i e 193 , there is little published clinical data i clinical published is little , there utero , chronic kidn , chronic

y omen. Although GBS colonization of the urinary tract in pr tract urinary the of GBS colonization Although omen. omen h omen , and neurogenic bladder [ bladder neurogenic and , y y w w in c h omatic, GBS bacteriuria is an independent risk independent is an bacteriuria GBS omatic, , additional studies are required to estimate the threat the threat estimate to required are studies , additional gnant populations, est populations, gnant y e icantly [ icantly f “increased “increased gr bacterial report kn and rarely a for search laboratories reproduct CFU/ml) in urine is associated with ad with inis associated urine CFU/ml) Microbiol Spectr e been biased because only a subset of the of the a subset only because biased been e

gnant gnant gnant gnant 4 v wborn e e vised guidelines notes that this practice represents an represents practice that this notes guidelines vised a e yelonephritis, and antibiotic treatment of ASB has been demonstrated to reduce these risks risks these reduce to demonstrated been has ASB of treatment and antibiotic yelonephritis, aginal colonization test posit test colonization aginal urden of GBS UTI is a major public health concern [ concern health public major UTI is a GBS of urden e 10 of babies that found to disease compared con to been performed h Clearl prop and for screening of action course the best determine disease and GBS neonatal of 4% that study estimated One measures. v in be missed that could bacterium for the niche independent and distinct be could a tract p signi report should labs microbiology r Surprisingl GBS is the leading cause of sepsis and meningitis in n in meningitis and of sepsis cause leading GBS is the n reproduct the colonizing pr asympt [ GBS sepsis neonatal as as well chorioamnionitis un recommend Control prop antibiotic and of gestation pr in recommended also ASB is for treatment and Screening del preterm of risk higher at ASB are Among nonpr Among ind 100,000 per 4.4 cases approximately of ind conditions underlying Common malignan neuropat in nonpr by GBS caused in young GBS with associated UTIs of proportion the to In contrast UTI. or pneumonia, nonpr pr b U.S. the in annually wis e GBS bacteriuria in pregnan in GBS bacteriuria Kline and L

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209 n – gnan anism has not anism eral recent icant e icant e g ed di f v 1α), r elop an e elop e k - 202 e infection (4 infection e v and i and

disease in in at disease e v ely to be associated be associated to ely i l studies are needed l studies k xamined GBS GBS xamined as ylactic antibiotics at antibiotics ylactic e (MIP v h

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as gies are lacking in settings in lacking gies are v ]. Additiona ]. erity of GBS GBS of erity v e i n v actors to injure actors e f ants with i with ants e obser e f 213 v ]. A number of GBS virulence virulence of GBS number A ]. disproportionate number of acute of acute number disproportionate thus, relat thus, ystitis [ ystitis eral eme , the CDC recommends that recommends CDC , the a , w studies h w studies c y v e e microbe interactions in populations at populations in interactions microbe 25 211 - ylactic measures during pr during measures ylactic h ions using serotype III GBS strains in mouse mouse in strains GBS III serotype using ions ention strat ention ]. In the murine model, the presence of GBS GBS of presence the model, murine In the ]. v ariety of GBS serotypes are associated with with associated are serotypes GBS of ariety did not appear to h to not appear did UTI [ UTI e

y should be g be y should

e demonstrated that sialic acid residues of the of the residues acid sialic that e demonstrated v c v une responses 212 e GBS disease. Attempts to d Attempts disease. GBS e ut only a f only a ut a , v times more frequent than GBS neonatal infections infections neonatal GBS than frequent more times b atality rates for rates i atality coli i m

- f gnan as E. e 211 v ytolysin , n ailable in PMC 2016 June 01. c v ]. These clinical studies h studies clinical These ]. as found to cause a a cause to found as wn that a a 25 . Case o w xperimental studies h studies xperimental y 183 e ariety of body sites (skin, soft tissue, lung, peritoneum, peritoneum, lung, tissue, soft (skin, sites body of ariety , we will 1) discuss s 1) discuss will , we r , v

r e sh . e v y ], macrophage inflammatory protein inflammatory macrophage ], e pathogens of the urinary tract, 2) introduce s 2) introduce tract, urinary the of e pathogens v a actors of importance in the urinary tract and to understand the the understand to and tract urinary the in importance of actors

v y time in pr y time e f er i y n v hemolysin/ ]. These studies h studies These ]. l w i 212 - chapte [ o

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213 posit o - 1α v , ]. H ]. i - Author manuscript; , and biochemical details details of host biochemical , and

elderly (~15%) compared to young in young to compared (~15%) elderly r . 39 actors may play important roles in this cont this in roles play important may actors e been successful in early trials in animals and humans [ and humans in animals trials early in been successful e 25 f , v al foll al a , serotype III GBS GBS III serotype , , in contrast to screening and prop and screening to in contrast , xtens 25 r r iv e 10 [ 10 e e - v v actors by inoculating wild type and mutant strains of bacteria into the mouse mouse into the of bacteria strains mutant and type wild by inoculating actors characterized in other models, models, other in characterized e e f s and induction of host im of host induction s and r of labor and del and of labor ], whereas the β the whereas ], w w

, molecula o o elderly patients are at risk of i at risk are patients elderly accine h accine r 25 v partum periods, similar screening and pr and screening similar periods, partum - Microbiol Spectr e been been e ]. H ]. ustly induces IL induces ustly 9, and IL 9, and - v b a xperimental studies of GBS urinary tract infect urinary tract GBS of studies xperimental 10 urinary tract [ tract urinary urinary GBS in the of establishment for optimal are necessary polysaccharide GBS capsular [ tract surv bacterial virulence GBS to identify cellula disease. GBS risk for of this remainder In the Gram underreported UTI. H UTI. li more were which serotypes, other to disease compared symptomatic [ bacteriuria with asymptomatic e [ infection of transurethral models ro IL GBS during bladder in the inflammation histological to compared responses transcriptional h virulence groups. a at infections cause GBS can virulence of range a wide utilizes etc.) and tract, urinary [ meningitis) osteomyelitis, bacteremia, (e.g. infection in disseminated resulting tissues, kn is much Although been studied virulence which h analyses Epidemiological the time 10 approximately GBS is by UTI caused elderl the among and is common the among higher [ post where GBS s and incidence the in reductions future of the possibility routine third trimester screening procedures. Currentl procedures. screening trimester routine third a at bacteriuria GBS with wis e asive GBS disease in the elder disease in GBS asive v n GBS virulence facto GBS virulence I Kline and L

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v omen omen [ indings, clinical clinical indings, v a single a single ], which is based based is which ], f astidious w

vidence vidence omen with omen f w o w in B w in e posit aginal microbiota microbiota aginal o w - e) v 220 vironment for vironment erse repertoire of repertoire erse aginal fluid, fluid, aginal gr v n v ]. H ]. v r i i aginal lactobacilli are at are lactobacilli aginal e ]. This This ]. v aginosis are more prone to prone more are aginosis ov 228 associated associated xamine xamine v - – 216 e fold increased risk of UTI of risk increased fold ydrogen peroxide, and other and peroxide, ydrogen ]. Clinical features of BV (i.e. (i.e. of BV features Clinical ]. - oman’s oman’s V – probiotic administration may may administration probiotic h ]. These studies are consistent are consistent studies These ]. wing that wing w

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v 217 - v ic mechanisms to discourage UTI UTI to discourage mechanisms ic agina [ agina ov i rs and a more d a more rs and xperimental models. While it remains a a remains it While models. xperimental f v e xclus e ]. Another method for BV diagnosi BV for method Another ]. xually xually act ]. Further supporting these these supporting Further ]. e stained slides where a higher score indicates indicates score higher a where stained slides 221 - – omen with bacterial bacterial omen with 216 y (s dominant population of population dominant – w h

indings raise the possibility that that possibility the raise indings 219

f y hanisms to enhance UTI susceptibilit to enhance hanisms h 214 Figure 2 (with emphasis on Gram emphasis 2 (with Figure xamining the association between BV between association the xamining e been described in the B in the described been e ailable in PMC 2016 June 01. w and other andother e v v aginosis (BV) and is often labeled as an ‘imbalance’ or ‘imbalance’ an as labeled is often (BV) and aginosis ywhere from a 2.2 from ywhere

xperimental models demonstrated that demonstrated models xperimental ed in both the female and male urinary tracts using using tracts urinary and male female the in both ed , a omen with more d more with omen a v n xpected inhabitants of the urinary tract using culture using tract urinary of the inhabitants xpected e v one of the common bacteria to bacteria one common the of e

w and cells’) [ cells’) , - e a wn wn mec omen and their babies [ babies their and omen v ginosis (BV) and UTIginosis (BV) and gues that the composition of a of composition that the gues o omen with a omen a r w microbiota. ely in recent years is the Nugent method [ method Nugent years is the in recent ely a ely to contain higher tite higher contain to ely v W k i V ]. Studies Studies ]. aginal fluid and the presence of epithelial cells studded with studded with cells of epithelial presence and the fluid aginal able 1, able bacterial bacterial aginal pH >4.5, ‘thin’ grayish homogenous homogenous grayish ‘thin’ pH >4.5, aginal aginalis v T v v e studies in studies e 223 xtens v , e Actinobacteria a vidence a vidence omen who are prone to recurrent UTI [ UTI recurrent to are prone who omen Author manuscript; e

. aginal microbiota because it has been associated with a wide a with associated been has it because microbiota aginal 222 w e also been obser been e also v vide compelling preliminary data that that data preliminary compelling vide v o a , our understanding of understanding , our y omen with BV h with BV omen Gardnerella w w pr aginal bacteria with UTI susceptibility in UTI susceptibility with bacteria aginal e’ molecules produced by lactobacilli may create may by lactobacilli produced e’ molecules o icial for for icial v , these results suggest a possible linkage between dysbiosis of the v independent approaches. These These approaches. independent f r i OH treatment of OH treatment e anaerobes, e anaerobes, criteria) include include criteria) - v ic ic K i f ], another possibility (though not a mutually a mutually not (though possibility another ], y of the bacterial genera that h that genera bacterial y of the w and illustrated in in illustrated w and Microbiol Spectr ed anaerobes in their urine than healt icient to yield clinical features and biochemical phenotypes of BV in a murine murine a in phenotypes of BV biochemical and features clinical yield to icient wer risk of UTI compared to to compared UTI risk of wer erse health outcomes for outcomes health erse at . Only recently h . Only recently o n f x o obiota, Bacterial obiota, Bacterial v g vironment h vironment f V r e n xperimental studies are needed to more fully understand the causal relationships linking linking relationships causal the understand fully more to are needed studies xperimental 229 e speci through speci act that lactobacilli possibility distinct [ unkn through act BV bacteria bel ma e culture be bene ab presented studies culture anaerobic of results with li more were UTI recurrent mi togethe bladder of the and dysbiosis Unfortunatel acid, lactic that It is thought limited. is infection tract urinary ‘defens the in uropathogens, including pathogens, potential upon ‘clue (i.e. mount wet in bacteria more used has been Gram using system scoring on a morphotype B bacterium, su [ model infection that found [ studied population on the depending n studies urogenital colonization states may influence the risk of UTI. the risk influence may states colonization urogenital clinical Mounting of UTI. risk her influences a l n as some by to is referred of the dysbiosis ad Amsel studies that demonstrate some un some demonstrate studies that 3) and urine, in detection bacterial for approaches independent wis e ginal Mic a V Kline and L

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f hemolytic, f l - oid life oid o This study r This study Denmark hospital yielded yielded hospital Denmark

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e been characterized as resistant as resistant characterized e been F r

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a i 230 ) UTI demonstrate that when patients when that UTI demonstrate Aerococcus [ species. The result is that aerococci are that aerococci result is The species. Aerococcus vide on 2 planes at right angles, angles, right at planes on 2 vide as

ely anaerobic, α anaerobic, ely i icant icant e and leucine aminopeptidase posit leucine aminopeptidase e and particula v anism, bacteriuria cleared and the patient the and cleared bacteriuria anism, f v

v is necessary to is necessary i n i g urinae

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y d ysiological similarities with lactococci, with lactococci, similarities ysiological atients with UTI caused by by UTI caused with atients ositive and and ositive month period in a in a period month at v e - h P urinae e g

P ]. In ]. viridans bacterial identi bacterial e

- ]. ]. can cause urinary tract infections and urosepsis, urosepsis, and infections tract urinary can cause n A.

- acultat A. f 238 ely contaminants. ely 237 GPC card, bioMérieux) to correctly identify 30 identify correctly to bioMérieux) card, GPC k Aerococcus of sanguinicola -

]. Molecular tools such as ampli as such tools Molecular ]. ainst the o ainst Aerococcus g Aerococcus A. ferent species of species ferent ailable in PMC 2016 June 01. f v pathogen in susceptible ind in susceptible pathogen 239 and the potential uropathogen uropathogen potential and the a e a

, v , we present s present , we and i anisms [ anisms e urological abnormalities or other risk risk other or abnormalities urological e r ted Gram

Aerococcus and oxidase and , g v xception

r r a ication of of ication - e f o fect

f ication of of ication y h gular clusters. Species of of Species clusters. gular f ging, or underreported, including species of of species including underreported, ging, or e” of detection by standard approaches. by standard detection of ]. Case reports of reports Case ]. n r e k repo li viridans - A, which are not commonly empl not commonly are which A, -

r 241 , and VITEK 2 ID 2 VITEK , and N and viridans group streptococci h streptococci group andviridans y of the cases described are i are described cases y of the getation, and are also common isolates from the human the human from isolates common also are and getation, , P A.

n

ve Author manuscript; Actinobaculum

. 240 eral species of eral species w discrimination [ discrimination w antibiotics e antibiotics v o ied and/or discarded as li as discarded and/or ied f e ]. Ma ]. e a number of biochemical and p ofbiochemical e a number v urinae,

is isolated from blood along with signi blood along is from isolated isolates (with the is a genus of microaerophilic, of is microaerophilic, a genus characteristic of aerococci is that th that is aerococci of characteristic a

Aerococcus 237 “ A. anisms may be missed as causes of UTI due to 1) misclassi due to of UTI causes be missed as may anisms , Aerococcus xt section of this chapte xt section

g , dust, and , dust, r e r , ID 32 STRE , ID 32 e cocci that are catalase are that e cocci ied with l with ied P 233 f v i , Microbiol Spectr anisms associated with BV could play a more direct role in the etiology of host etiology in the role direct more a play could BV with associated anisms wth of wth of o g r xamined the ability of three commonly used used of commonly three ability xamined the 230 ging, and Unde ging, and sequencing of 16S rR of sequencing accurate identi for needed are misclassi often identi and accurate Prompt potential by this infection systemic of isolates UTI. Most uncomplicated [ to sulfonamides with are treated [ Aerococcus h Aerococci [ streptococci and enterococci, pediococci, between tests. phenotypic routine using them between to distinguish e STRE di representing isolates tract urinary Aerococcus identi Aerococcus posit unique One irr and tetrads in resulting ai from S tract. urinary including a 4 during cultured urine specimens of all 0.8% gr and ma often elderly most In the n In the eme rare, that are bacteria Corynebacterium, o These signi of 2)dismissal criteria, phenotypic distinguishing or 3) lack contamination’, o tract. the urinary within interactions uropathogen as a cause of UTI of as a cause r wis , Eme e e ococcus ococcus r Ae Rar of UTI Etiologies Kline and L

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v e spectrum spectrum i

xperiencing no no xperiencing is treated byis treated - v or to cause encrusting encrusting to cause e irst described in described irst ].

e group D2) is the group is D2) f e urealyticum w

k Actinobacteria, o li 249 because the o the because - C.

acultat f ystitis and occur due to due and occur ystitis were ]; h ]; c ersion of urea to ammonia to ammonia of urea ersion are nonpathogenic. The The are nonpathogenic. e patients e patients

251 v as not recognized or e or as not recognized v anism [ anism urealyticum i , n

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250

yelitis, a chronic inflammatory inflammatory a chronic yelitis, ycline, ciprofloxacin, ofloxacin and ofloxacin ciprofloxacin, ycline, ]. Actinomyces p c encrusting Corynebacterium UTI also report that Gram UTI that also report urinae microbiota,” since it is generally is generally since it microbiota,”

, similar to other other to , similar

r diptheriae , with acute and chronic infections of infections chronic and acute , with

243 spore forming, forming, spore e y - , A. Corynebacterium urealyticum C. wed that 9.8% of renal tran of renal 9.8% that wed ov

]. ]. wn as o ampicin [ ampicin f vious treatment with broad with treatment vious o ]. 242 e , 245 ystitis and ystitis wth on blood a blood wth on , ication of the urinary tract, and treatment with with treatment and tract, urinary of the ication c 250 o realyticum Actinobaculum

f urealyticum 240

vious urological procedure and/or mucosal lesion mucosal and/or procedure urological vious ystitis caused by ystitis u vided, patients often progressed from simple UTI UTI simple from progressed often patients vided,

e eloping alkaline encrusted UTI. While this type of type this While UTI. encrusted alkaline eloping , c o 244 motile, non motile, v C. other than - irst detection of the o of the detection irst C. e e study sh e study f e bacilli and polymorphonuclear cells, despite routine routine despite cells, and polymorphonuclear e bacilli , which catalyzes the co catalyzes , which e. Molecular detection techniques can also be also can techniques detection e. Molecular v 235 viously kn viously ailable in PMC 2016 June 01. v y i v ut there is strong suspicion of encrusting of encrusting suspicion strong is ut there i , v e i anisms described as described as anisms b a

vit at g i splitting bacteria such as as such bacteria splitting r e, non (pr e, g - 234 v e v posit i i - Alkaline urine and the presence of struvite crystals in urine in urine crystals of struvite presence the and urine Alkaline

Encrusting Encrusting at

in urine, with nearly half of posit half of nearly with in urine, ]. . g and the species e

posit - , in other situations when when situations other , in 248 r Corynebacteria e – as not promptly pr promptly notas v e

urealyticum w eals Gram eals

ycline, erythromycin, and ri and erythromycin, ycline, 246 w Author manuscript; v c

al of encrustations, acidi ofal encrustations, . o e C. v y [ term hospitalization and/or pr and/or hospitalization term urealyticum urealyticum are Gram o -

infection can often be missed in routine urine culture urine routine in be missed often can infection

that are common components of the skin microbiota and increasingly increasingly and microbiota skin of the components that are common h

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requires at least 48 hours of gr of 48 hours requires least at yticum antibiotics. A number of reports document resistance of resistance document of reports A number antibiotics. l Actinobaculum xpression of urease act urease of xpression wing the isolation of o of the isolation wing n dioxide. The presence of a pr of a presence The n dioxide. e systemic infections [ infections e systemic e o wing and requires enriched media. More media. enriched requires and wing v i o haalii yed when tests are n are tests when yed gone long as ered fully; h fully; ered c o r v Microbiol Spectr n ov urealyticum w gr w

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e uting to this interpretation were collected (e.g. during UTI or prior to UTI). to prior or UTI during (e.g. collected were interpretation uting to this ov , v y b a rel - xamples of patients were pr were patients of xamples e els of bacteria such such bacteria of els independent denaturing high performance liquid chromatograp liquid performance high denaturing independent corresponding of the detection and method based - - v e for leu e e v i Microbiol Spectr anisms obser anisms ely to h to ely g k r aginal bacteria may inhabit the female urinary tract [ urinary tract female inhabit the may bacteria aginal aginal bacteria. The authors state that standard cur that standard state authors The bacteria. aginal routine methods. The authors concluded that catheterized patients who had a UTI were more more were a UTI who had patients catheterized that concluded authors The routine methods. li h not who did data contri d if higher clear not it is Thus, dr UTI of a presence the UTI or if b to demonstrate attempt In an in were tract adult asymptomatic from urine of composition bacterial v address adequately not does catch”) “clean (midstream method collection that the studies is with urine contamination of the possibility of line One by urine contamination of a product simply rec bacteria [ approaches r currently that are bacteria studies, high l polymicrobial, and polymicrobial, (see ab BV with associated lactolyticus of renal urines Fusobacteria posit by urine contamination of possibility the to opposed UTI as ofsymptomatic the cause v ma in that and method DHPLC the using urine CFU in to estimate clinically d bacterial assess o detection). independent’ In one stud culture PCR identify separate and [ urine specimens midstream from Interestingl UTI. risk for high culture that 9.2% demonstrate also signi contain to appeared yet approaches, culture of the Most approach. the DHPLC aerobic conditions used for urine culture. culture. for urine used aerobic conditions h that studies microbiome wis e Kline and L

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f , arding a condition (UUI) of uncertain etiology uncertain of (UUI) condition a arding ferent from from ferent r ferences obser ferences 292 f iles. Thus, subsequent studies used cathete used studies subsequent Thus, iles. g , the authors also performed E performed also authors , the f f 327 e y , Lactobacillus in their bladders compared to to compared bladders in their 0.05). Di 0.05).

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1037. [PubMed: [PubMed: 1037.22417256] , Buba , Buba ago it it ago P , B , 847. [PubMed: 847.16107984] [PubMed: F – arada arada J Kay SA. Diagnosis and management of uncomplicated urinary tract infections. Am infections. Am urinarytract of uncomplicated Diagnosis management SA. and Kay est Ethiopia. BMC Res Notes. 2014; 7:481. [PubMed: 25073620] Notes. [PubMed: 7:481. Res BMC est 2014; Ethiopia. T – - ws SJ, Lancaster J Lancaster SJ, ws P , it is widely held that Gram that held widely , it is ed, 3) summarized recent literature suggesting that a wide a wide that suggesting recent literature summarized 3) ed, ysical health outcomes: a systematic r ysical a outcomes: health systematic e , y W A. Urinary tract infections in pr infections tract Urinary A. h P k ranspl. 2014; 25:85 ranspl. 2014; ards MS, Ba ards MS, term care setting: is the multireagent strip an adequate diagn adequate an strip setting: is the multireagent term care e uropathogens in the urine are li are urine the in e uropathogens e bacteria. bacteria. e g RC, Underland Underland g RC, T - T v r w v i i ysician. 72:451 2005; agenlehner FM, Naber KG. Current challenges in the treatment of complicated urinary tract complicated urinarytract of treatment Currentin the challenges NaberFM, KG. agenlehner Microbiol Spectr 41:839 Pharmacothe on p Dis. 2001; 7:342 155:14 1995; Intern Med. hospitalized medical patients. Arch h at viously appreciated and also may impact pathologic outcomes in the urinary tract. urinary in the outcomes pathologic impact also may and appreciated viously North Dis P 2010; Res. 21:297 Infection. Biomed long 2009; 48:227 3):67 Infect. 12(Suppl Microbiol Clin infectionsprostatitis. and 366:1028 in in urinalysis infection urinary tract for [PubMed: 26009628] 24841169] pr infection among tract predict urinary o assumptions h o assumptions erloo g W e e

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a 206:952 g PubMed: PubMed: 17785483] – associated urinary tract infection is rarely symptomatic: a rarely symptomatic: is infection tract urinary associated - r ilms: surv ilms: f oo JM, Lee SJ. A n oo Lee JM, SJ. aroni Sterbini , Hayes E, Caparon MG, Hultgren SJ. Enterococcus Enterococcus SJ. MG, Hultgren ,E, Caparon Hayes Y 293. [ 293. P

wis WG, L wis WG, SJ, Hultgren W – 605. [PubMed: [PubMed: 605. , . Bio e eals roles for Ssp and SdrI in virulence. Infect Immun. 2010; 78:1943 2010; Infect Immun. SdrI in for and virulence. Ssp eals roles – F

gnated urinary catheters in trauma patients: a randomized trial. Ann randomized a urinaryin trauma catheters gnated patients: ord B, Caparon MG, Hultgren SJ. Enterococcus ord MG, Hultgren SJ. B, Caparon inatorial small v 4175. [PubMed: 4175.20696830] [PubMed: e W F e – yon yon

L associated urinary tract infections. Infect Dis Clin North Am. 199 Am. North Dis Clin Infect infections. tract associated urinary - MA, Nielsen Nielsen H MA, Mathur M, Go Mathur

r impr 15:167 2002; .

- v , Bugli e P Author manuscript; artz DJ, L

. ede M, Looms D, Lippert FK, Dahl B, Tønnesen E, Rasmussen LS. Infection risk risk LS. Infection Tønnesen E, Rasmussen Dahl D, B, FK, Lippert ede Looms M, aecalis, aecalis, EfbA, is important for virulence in a mouse model of ascending urinary arner M, Speller DC. In 116. [PubMed: 2909483] [PubMed: 116. w v f mediated inflammation to establish urinary tract infections. Infect Immun. 2013; Immun. Infect infections. tract establish urinary to inflammation mediated vić Cathete A, M. Hukić – - W ys in the urinary tract of C57BL/6J mice. Infect Immun. 2005; 73:2461 Infect mice. Immun. C57BL/6J of the urinary tract ysin o e , . 1997; 40:604 1997; . andit andit D,

A, Maki DG. A, Cathete DG. Maki . Cathete. P e study of 1,497 catheterized patients. Arch Intern Med. 2000; 160:678 Arch Intern Med. 2000; patients. e catheterized of 1,497 study r P P 4745. [PubMed: 22733070] 4745. [PubMed: 3595. [PubMed: 21690238] 3595. [PubMed: , Nallapareddy SR, Murray BE. Importance of the ebp 131. [PubMed: 131.18453274] [PubMed: v Martin SM, SM, Martin associated urinary tract infections in mice. Antimicrob Chemothe Agents mice. Antimicrob in infections tract urinary associated W i 339. [PubMed: 339.23132492] [PubMed: – – – V , Choe HS, Lee DS, Lee DS, , HS, Choe - Ljub r ution to uropathogenicity in unobstructed urinary tract infection of rats. Infect Immun. rats. Infect of infection tract unobstructed urinary in to uropathogenicity ution – - Y b wis K. Multidrug tolerance of bio tolerance Multidrug wis K. arren arren J e orelli R, Serror ambyah ambyah Microbiol Spectr virulence in an optimized murine model of foreign body foreign model of murine virulencein an optimized 2010; 78:4166 Immun. foreign body 81:329 Comb SJ. MG, Hultgren cathete 56:4738 by group B streptococcus in a murine model of urinary tract infection. Infect Immun. 2011; Immun. Infect infection. tract of urinary model a in streptococcus by murine group B 79:3588 for the kidn [PubMed: 15784592] associated pilus) locus in the pathogenesis of Enterococcus infection. Dis. 195:1671 J Infect 2007; Martini C, Giard JC, Sanguinetti M, Posteraro B. The Enterococcus Dis. tract J Infect 2012; infection. 47:1259 Nephrol. 2015; infection. Urol Int infection in catheterized patients. Indian J Med Microbiol. 2001; Microbiol.19:132 2001; J Med Indian infectionin catheterized patients. 17664815] isolates of Streptococcus pneumoniae, Stap Chemothe contri 1989; 57:110 of n a Characterization SJ. MG, Hultgren r urinaryinfection tract 20176795] 1951. [PubMed: 622. [PubMed: 9378926] 622. [PubMed: with nitrofurazone Intern147:285 2007; Med. R Clin Microbiol 322:107 9:2 Basic Med injuries.2009; spinalcord Sci. Bosn J tract urinary to with reference special clinical specimens from species isolated enterococci of prospect 10724054] T W T 30. Guiton PS, Hung CS, Hancock LE, Caparon MG, Hultgren Caparon MG, Hung CS, Hancock LE, 30.PS, Guiton Hannan TJ, 31.PS, Guiton K Dodson CK, KA, Kline 32.Cusumano PS, Guiton 26. Kau 26.AL, Kau 27. Singh K 28. 29.H Kim 22. Johnson A R. Stap Marre John J, 23. S, Gatermann Ingersoll 24. Kline KA, Sch 25. Kline KA, 16. T 17.J, Stensballe Costerton J 18. RM, Donlan 19. L 20. Dedeić 21. PJ, Desai 15. wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

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e stap v gistic gistic induction of urease i r

at g . Bacterial colonization on colonization on Bacterial . e resistant coagulase resistant T - n

- ed: 21637845]

yticus. J Clin yticus. J Clin 444. [PubMed: 15780351] [PubMed: 444. 128. [PubMed: 3616271] [PubMed: 128. h –

7965358] yticus: a frequent cause of acute acute yticus: a frequent of cause associated urinary tract infection infection tract associated urinary - h 842. [PubMed: 2778465] [PubMed: 842. r

athol [B]. Immunol Microbiol Scand of microbiologic colonization of microbiologic colonization of – common cause urinary tract of common anisms and on urine constituents of the anisms P g 5:123 271. [PubMed: 271. 6833480] r community crystalline communitycrystalline bio independent microbiological analysis of analysis microbiological independent – - - yticus bacteriuria in Israel. Infection. Infection. 2006; yticus Israel. in bacteriuria xperimental ascending mi ascending xperimental h e wis AL. Immune modulationgroup B Immune by wis AL. ed athog. 2015; 11:e1004601. athog. 11:e1004601. 2015; e onogi K. onogi Enterococcus K. x P k . 2005; 65:440 . 4541. [PubMed: 7927719] [PubMed: 4541. 2979. [PubMed: 1452668] [PubMed: 2979. , O y yticus a as – uckwell LA, Hilton AL. Urinary tract infection in Hiltoninfection tract Urinary AL. LA, uckwell yama Tsukamoto K, – T h e ylococcus saprop T k h a 1557. [PubMed: [PubMed: 1 1557. ylococcus saprop T – h y HL. Increased incidence of urolithiasis and bacteremia 291. [PubMed: 291.2815452] [PubMed: e – 337. [PubMed: 337.6377440] [PubMed: wis AL. Impact of host age and parity on susceptibility to on susceptibility and age parity wis AL.host of Impact aeruginosa aeruginosa in . Urolog ace NR. ace NR. Culture e bacteriuria and obstruction of and long obstruction bacteriuria e e – r 1532. [PubMed: 1532.24280366] [PubMed: v A. Ascending urinary tract infections in rats induced by rats induced in infections tract Ascending A. urinary P ibility to urinary tract infection by uropathogenic Escherichia Escherichia by uropathogenic infection tract to ibility urinary amazaki amazaki i – . Ultrastructural .study Ultrastructural P ylococcus saprop ailable in PMC 2016 June 01. Y 4194. [PubMed: 22988014] 4194. [PubMed: h v 581. [PubMed: 9378923] 581. [PubMed: W

a – – 2217. [PubMed: 3320089] 2217. [PubMed: videncia stuartii coinfection due to syne posit –

a murine model. PLoS One. 2014; 9:e97798. [PubMed: One.24835885] 9:e97798. PLoS 2014; murine model. a - , Stephens M, Stephens , o

and Proteus mirabilis. Acta Proteus mirabilis. Acta and akahashi S, akahashi P

T enshtock B, Chazan B, Raz R. Epidemiology and clinical clinical and R. Epidemiology Raz B, enshtock Chazan B, ylococcus saprop ep A, Mobl y HL. Preferential use of central metabolism in metabolism v central of Preferential yuse HL. v , h , Coates AR. A model of Coatescathete A model of , AR. e Y 209:1524 a ersity of SCCmec elements in methicillin of ersity SCCmec elander Stap B. Y Y . 1989; 34:284 1989; . ilms. PLoS One. 2009; 4:e7811. [PubMed: 19907661] ilms. PLoS with Stap with v T

f i y yticus . Urease h . Scand J Prim Health Care. 1987; Health Prim 1987; Care. J Scand . Archer GL. Colonization of the female genital tract with Stap tract with genital of the female GL. Colonization Archer y W A, Costerton Costerton J A, A. Stap J P

Etherden I, Mårdh Etherden I, y Dror S, K - unishima unishima e ace of urethral cathete ace of urethral Author manuscript; - artz DJ, Gilbert NM, Hultgren SJ, L artz DJ, Gilbert NM, L artz DJ, Gilbert NM,

f . K arren J 350. w w en v Infect Dis. 1984; 6:328 Dis. Infect 1984; v wn – ilson SS, St Amand ilson SS, St Amand AL, e o W K A, Sellin MA, Gill W

a M, W omen, with special reference to Stap to with reference omen, special

350. [PubMed: 350.580432] [PubMed: 281.17033753] [PubMed: w yticus.Clin 1992; 30:2975 Microbiol. J . J Dis. Infect 2014; J . a – – w h y y HL, ylococcus saprop ylococci clinical isolates. PLoS One. 2011; 6:e20191. [PubM ylococciPLoS isolates. clinical e h el D JC, h y catheter bio urinary eliusMårdh B, vit ere urinary tract infection infection in eretract urinary k i e v allmark G, Arremark I, Arremark I, allmark G, ov unin CM. Blockage of urinary catheters: role role of microo Blockage urinary catheters: of unin CM. yelonephritis caused by Pseudomonas yelonephritis caused by Pseudomonas e Microbiol Spectr stap young 31:348 saprop patientscharacteristics of 34:278 SwedenIEpidemiolog catheters. J Med Microbiol. 2007; 56:1549 Microbiol. 2007; catheters. J Med fol Microbiol.17:267 urinary 1983; tract J Clin specimens. 1997; Am. 11:551 Dis Clin North 138:791 1978; Infect Dis. outpatients. J among female urinaryinfection tract 739158] R infections. Streptococcus influences Streptococcushost influences suscept 80:4186 2012; Immun. coli. Infect s 102:67 Int. 2008; tip. BJU catheter of the contamination bacterial initiated by 18284413] intraluminal sur urinarycatheters. Urolog nutritional basis for polymicrobial infection. PLoS infection. for polymicrobial basisnutritional 25568946] during Proteus mirabilis and Pr act 42:835 1989; Epidemiol. J Clin formation encrustations. of J Clin 25:2216 1987; Microbiol. p 1994; 62:4534 Immun. Infect infectionin mice. Stap 1987; 95:347 W K

51. Gillespie 51. Gillespie DE, 52. Soper Rupp ME, 53. Colodner R, northern in care health primary infection in tract B. LG, Urinary Mattsson 54.Burman Ferry S, 45. Frank 45.DN, Frank coagulase of Hoban GK. Characterization Harding SA, 46. LE, Nicolle Infect infection. urinary tract of uncomplicated andWE. Diagnosis treatment Stamm TM, 47. Hooton 48. 49. H Lü D C, 50. X. Z, Peng Zong 39. Kline KA, Sch 39. Kline KA, Sch 40. Kline KA, K, Anson Hu 41. JM, Barford 42. Matsuk 43. Nic in mi interactions DJ. Species Stickler SM, 44. Macleod 34. Alteri CJ, Himpsl SD, Mobl CJ, 34. Himpsl Alteri 35. Armbruster CE, Smith SN, 36. 37. Mobl Shino A, N, R, 38. Hayashi Tsuchimori 33. Hjelm E, Lundell33. E, Hjelm wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

.

r age 29 - yticus. P 2068.

onno h

K Y R 3896. f pathogens f pathogens – lactam lactam -

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h . Methicillin y occurrence of 980. [PubMed: 980. p Int J Antimicrob Int J c T – ibronectin. Infect omen omen caused by omen omen in primary 5 f fusion test for the test for the fusion amashita N, f

w eillance Program, w ylococcus Y ylococcus ylococcus st response st response to v h . 2008; 52:2061 2008; . h

r ylococcus ylococcus saprop yticus. h

h ylococcus ylococcus cassette h

ukata K, ukata K, b 516. [PubMed: 6563036] [PubMed: 516.

– xperimental urinary tract infection infection tract urinary xperimental yticus: role in urinaryyticus:tract in role

e h ylococcal cassette chromosome mec chromosome cassette ylococcal h properties. Mol Microbiol. 1998; Mol properties. ylococcus aureus. Antimicrob Agents Agents ylococcus aureus. Antimicrob a S, Ichimura S, Ohta Ohta S, a Ichimura S, yticus in the aetiology of nongonococcal of aetiology in nongonococcal yticus the h 3066. [PubMed: 3066.6644988] [PubMed: Agents Chemothe Agents h

245. [PubMed: 7986894] w – Y Antimicrobial Sur Y Antimicrobial a ylococcus saprop – S132. [PubMed: 11320452] R h – ylococcus frequen species: 128. [PubMed: 8792507] 128. [PubMed: h

– yticus binds hemagglutinin

y of the antimicrobial susceptibility o susceptibility y the antimicrobial of 185. [PubMed: 3273467] [PubMed: 185. binding protein supposed to cause high resistance resistance high bindingsupposed to cause protein h y J, Bell J, Jones RN, Beach M. SENT yM. RN, Beach J, J, Jones Bell ylococci: pathogens associated with medical ylococci: with pathogens associated medical - . Hemagglutinating and adherence properties of of adherence properties .and Hemagglutinating 41. [PubMed: 6695157] [PubMed: 41. – binding protein associated with beta with bindingassociated protein aluation of a cefoxitin disk di a cefoxitin of aluation k h - ve – v W ylococcussaprop vs 10817707] h e . E el e and autolytic and e T k 494. [PubMed: 6887362] 494. [PubMed: yticus 1990; J Med S. epidermidis. and Microbiol. v e stap i 374. [PubMed: 116708] 374. [PubMed: – 243. quiz 244 243. quiz h v – resistant resistant Stap i – umano umano M, Ohk - ylococcus ylococcus saprop w class of class stap genetic element, w achi M, Doi M, Inoue M, M, U achi M, Inoue Doi at h K e ailable in PMC 2016 June 01. g . Bacterial prostatitis caused caused by Stap Bacterial. prostatitis . Symptomatic urinary tract infection in infection tract urinary Symptomatic . , W v e P T T gion for the gion SENT for the a , ylococcus 167:97 aureus. J Bacteriol. 1986; n ococcus saprop ococcus e

- yticus isolates carrying stap isolates yticuscarrying F h g Stap a S, Ohta inity penicillin inity AMA. AMA. 1983; 250:3063

r h yl A. Urinary tract infections in men men caused by Sta in A. infections tract Urinary f J w f P h ic r ic A. infections due Stap due to infections a a adyk f [PubMed: 7090104] [PubMed: - P 1555. [PubMed: [PubMed: 1555. w w – aci e methicillin er U, Gatermann SG. The hemagglutinin of Stap of er U, The hemagglutinin SG. Gatermann o P y of v k 4563. [PubMed: 4563.7927721] [PubMed: yticus: epidemiology and virulence in virulence in yticus:and epidemiology yticus. i 578. – h h ylococcussaprop 504. [PubMed: 504.16697558] [PubMed: ve – h –

Bec

- posit r w VD, Z ylococcus aureus. J Bacteriol. 1984; ylococcus 158:513 aureus. J Bacteriol. estern - ace protein with adhes ace protein with a , Hiramatsu K. A n Hiramatsu , f h yer HG. Stap Author manuscript; ener Dis. 1979; 55:369 ener 1979; Dis. T W e

uroda M, Omura C urodaOmura M, uroda M, urodaOhk M, . aller MA, Schmitz Smay allerFJ, MA, Schmitz V ylococcus saprop f omasz A. omasz L K K engle h 76. [PubMed: [PubMed: 12493789] 76. T – , Ito , W yer HG, Gatermann SG. Cloning of aas, a gene encoding a encoding Stap of gene a aas, yer Cloning SG. HG, Gatermann . 2000; 44:1549 2000; . i M, Song MD, Ishino M, Song MD, Ishino i Y r ged in urogenital tract infections. Antimicrob urogenitalAntimicrob tract infections. ged in e

r 881. [PubMed: 881.9723925] [PubMed: 141. [PubMed: 141.2192064] [PubMed: . 1982; .19:576 1982; yticus is a major adhesin for uroepithelial cells. Infect Immun. 1996; 64:3893 1996; Immun. cells. Infect for uroepithelial yticusa adhesin major is yticus sur yticus. Scand J Infect Dis. 1984; 16:37 yticus. 1984; Infect Scand Dis. J art LA, Rigby RC, Elliott TS. The pathogenesis of urinary tract infections associated with infections urinary tract of The pathogenesis Elliott TS. Rigbyart LA, RC, lactam antibiotics in Stap antibiotics lactam y – – - h h h , M , g 1999. Clin Infect Dis. 2001; 32(Suppl 2):S114 2001; Infect Dis. 1999. Clin ylococcus saprop ylococcus saprop – W fman CA, Hertz CS, Stap Sheagren JN. Hertz CS, fman CA, h h ema DJ, P ema DJ, ag elius B, Colleen S, Mårdh Mårdh eliusColleen S, B, elius B, Thelin I, Mårdh Mårdh eliusThelin I, B, f e eme ashide M, ashide M, ashide M, ashide M, k T yer HG, rats. FEMS Microbiol Immunol. 1988; 1:179 1988; Microbiol Immunol. rats. FEMS v g g

e ov ov artcipants Group. Sur a Microbiol Spectr saprop [PubMed: 8751944] 1994; 62:4556 Immun. saprop 29:871 Stap of M. Molecular cloning of the gene a the gene of of penicillin M. cloning Molecular to beta 3638304] Stap in mec, resistance chromosome encodes methicillin Chemothe resistant Stap h [PubMed: 18362191] Stap Escherichia coli, 32:135 from uncomplicated urinary tract infections: the ECO.SENS Project. J Antimicrob Chemothe the ECO.SENS Project. infections: tract urinary uncomplicated J Antimicrob from 2003; 51:69 P Latin America, States, Canada, collected the United in isolates of susceptibility and antimicrobial Europe, the and 1997 detection of mecA Agents. 27:500 2006; resistance Stap in Urolog 130:493 1983; J Urol. men. infections in saprop ho to in relation aspects diagnostic and clinical health care. Bacteriological, 14:122 1996; Health Care. J Prim infection. Scand Dis. 19:231 Infect 1994; progress. Clin Stap urethritis. Br urethritis.J Br 70. M M 71. S, Gatermann 72. Hell J, Hen Heesemann R, Marre 73. S, Gatermann 67. Katayama 67. Katayama 68. Hi 69. Mc 63. Die 64. Hi BJ, 65. Hartman 66. Matsuhash 57. Kau 58. H NorrbySandbe RS, 59. B, Jellheden Coagulase GL. 60. Archer Rupp ME, adult in young infections WE. tract Urinary RH, Running K, 61. Stamm Latham sur An international G. 62. ECO.SENS. Kahlmeter 55. H CC, McGr 56. Carson wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

-

64. 64.

94.

– age 30

– P

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1060.

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e ibronectin, ibronectin, ylococcus 2280.

v f e bacteria. i h – ylococcus PubMed: v i ylococcus h . 2000; . at

h y g tap ied in ied e f 2852. [PubMed: 2852. n – - 645. [ 645. posit - – ytokines to protect the to ytokines the protect 1175. [PubMed:

c 6428. [PubMed: – and binding domain A of – g ace Protein of f ashide M, Maruyama A, Maruyama ashide M, A, ace proteins GspB and GspB ace Hsa proteins , Shepherd M, Gatermann SG, SG, M, Gatermann , Shepherd oster TJ, Höök M. The oster TJ, serine Höök f g P

F , A, Schembri MA. UafB is a a is A, MA. UafB Schembri associated protein of protein associated P P -

ariation among Stap among ariation characterization of a characterization sur v a K, Hi ace MS Microbiol Lett. 2009; Microbiol 299:60 Lett. MS Rich Rich Sur anchored protein of anchored S protein f - w - accessory Sec [corrected] systems. Mol systems. [corrected] Sec accessory , Núñez G. Cutting edge: crohn’s edge: Cutting ,G. Núñez a ace display in ace display Gram -- binding protein. Infect Immun. 2006; Immun. Infect protein. binding Y yticus. Microbiol Res. 2015; 172:88 15501784] . Whole genome sequence of sequence . genome Whole f all - . 2011; .157:1161 2011; h T ay 1139. [PubMed: 1139.22411983] [PubMed: w y yticus that mediates binding to yticus to mediates binding that – w

h yticus. Infect Immun. 1992; yticus.60:1055 Infect Immun. ication and and ication h aspartate repeat protein identi aspartate repeat serine. FE , a Serine f . J Immunol. 2011; 187:2849 2011; J Immunol. . - - P y , Ogura collagen F 685. [PubMed: 12409048] [PubMed: 685.

– terminal terminal repeat and the li ylococcus Microbiolog epidermidis. - 13277. [PubMed: 16135568] 13277. [PubMed: h xport. J Bacteriol. 2004; 186:638 2004; J Bacteriol. xport. – e umano umano M, Morik 6537. [PubMed: 6537. [PubMed: K

– otsika M, Heras B, Simerska M, HerasSimerska otsika B, yticus as the cause of infected urinary calculus. Ann Intern yticus calculus. Ann as infected urinary the cause of

. The N ailable in PMC 2016 June 01. T ydrate epitopes on the platelet membrane glycoprotein membrane glycoprotein ydrate on the platelet epitopes h athogenesis of infections due coagulase of due to infections athogenesis T v h ylococcus saprop anner Identi G. a P eals the pathogenesis of uncomplicated urinary tract infection. urinary eals of uncomplicated the pathogenesis a H, h ark JH, Chen a lipase. Infect Immun. 2005; 73:6419 Immun. a Infect lipase. . Genotypic and and phenotypic . Genotypic ylococcussaprop induced lethalit induced v nç

W w - P h ι e T a amily in amily Stap w twist on an old path on old an w twist f e uhara S, Hattori M, Ohta Hattori M, uhara S, vis S, Eidhin DN, Lina G, Speziale Speziale DN, Lina G, S, Eidhin vis ydrophobicity of S. saprop our NL, K a h k 302. [PubMed: 302. 18544071] aecalis , Sullam PM. The Streptococcus gordonii platelet binding protein GspB binding gordonii platelet The PM. Streptococcus , Sullam – f yticus is a strain 7108, yticus is yticus r otsika M, Ulett GC, Alm RA, Alm Manning Ulett GC, M, otsika , Sullam PM. PM. Role of Sra , Sullam arner N, h h h W T F M. A n M. A 343. [PubMed: 3871598]

oh H, oh H, ed in W A, Sullam PM. The Streptococcus sur gordonii ThePM. Sullam Streptococcus A, –

v T J ylococcussaprop obser D, Sak ol , Ben Za , Ben hita Hirak A, h v T Author manuscript; W wski M, Ebsen M, Gatermann SG. The The SG. sur M, Ebsen Gatermann wski M,

n . o human cells. uroepithelial Microbiolog human

w MH, w MH, amas , Hartford O, Hartford , D a . Stap . ozn r Y

1546. [PubMed: [PubMed: 1546.10878118] Acad Sci USA. 2005; 102:13272 Sci 2005; USA. Acad W A, López A, A, Gibson B A, W , Braunstein , Braunstein – 4623. [PubMed: 16861649] 4623. [PubMed: B B , Michalski N, Kleine B, Gatermann SG. The uropathogenic SG. species Stap Gatermann B, N, , Kleine Michalski , Kleine B, Gatermann SdrI, a SG. Gatermann serine B, , Kleine , rans R Soc Lond B Biol Sci. 2012; Sci. 367:1123 Soc B 2012; ransLond Biol R – , Sakinç , Beatson SA, associated Nod2 mutation limits production of proinflammatory of limitsproinflammatory production Nod2 mutation associated yticus of a concentration D high tolerates yticus associated with linoleic acid resistance. BMC Microbiol. 2012; [PubMed: 12:8. 2012; Microbiol. BMC resistance. yticusacid associated linoleic with yticus from human and animal isolates. BMC Res Notes. 2010; [PubMed: 3:163. Res Notes. yticus human and BMC isolates. animal from , Matoba K, , Matoba W - T T T P P f C, Peters G, Heilmann C. Heilmann G, f Peters C, T rich repeat adhesin of Stap adhesin of rich repeat wind O, Missiakas DM. Protein secretion and sur secretion O, Protein Missiakas DM. wind h h h f Y - e ylococcus aureus, in binding to human platelets. Infect Immun. 2005; 73:2273 Immun. Infect2005; platelets. ylococcusto human in aureus, binding ylococcus saprop ylococcus saprop ylococcus saprop goes glycosylation independently of goes independently glycosylation ylococci. Lancet Infect Dis. 2002; Dis. 2:677 ylococci. Infect Lancet r h h h h h wler JE J wler JE uroda M, uroda M, o on Ei on ibrinogen ibrinogen and Microbiol Spectr [PubMed: [PubMed: 25497915] stap (Sdr) protein aspartate repeat 146:1535 Med. 102:342 1985; saprop [PubMed: 19674114] mediate binding to sialylated carbo to sialylated mediate binding 2004; 72:6528 Ibalpha. Immun. Infect Stap [PubMed: 15784571] disease host Enterococcus from 21849681] Microbiol.69:291 2008; SdrI protein is i serine f 21252279] cell a of MA. Characterisation BeatsonSchembri SA, saprop 22243671] Stap 74:4615 unde 14729688] associated protein (Ssp) of (Ssp) Stap associated protein [PubMed: 1541520] Stap 16177313] Philos Inose Stap Proc Natl saprop 20537181] v McCrea K F K 88. 89. 90. 91. Sakinç 83. Bensing 83. Bensing H 84. Siboo IR, Chambers 85.YG, Sh Kim N 86. Rigel 87. Kleine B, Ali L, 80. King N 80. King 81. Sakinc 82. Bensing 75. Gatermann S, Kreft B, Marre R, Marre B, Kreft 75. S, Gatermann 76. Sakinc 77. Schne 78. N 79. King 74. Kleine B, Gatermann S, Sakinc Sakinc B, Gatermann S, 74. Kleine wis e Kline and L

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k , Hebel JR, Johnson DE, JR, , Johnson Hebel eidenmaier C, Mis 369. [PubMed: 18585915] [PubMed: 369. V an V W –

T , Hanada , ated MRSA. 13:1510 Nat MRSA. 2007; ated Med. encoded encoded ylococci. Mol Cell Probes. 26:99 ylococci. Mol 2012; Cell - 4626. [PubMed: [PubMed: 20639341] 4626. Y h ranscription and translation products of the and of translation products ranscription – C, Slic T a R, ylococcus ylococcus aureus bio e intracellular bacterial communities during A g h k associ - wicz MA, Dreisbach A, Back J li e antimicrobial action is e antimicrobial pr action elop their characteristic structure. Proc Natl Acad Sci AcadUSA. Sci structure. Proc eloptheir characteristic Natl - o ailable in PMC 2016 June 01. v agener MM, Obman A, agener Obman MM, v

i v 08; 16:361 e n RE, Rickard AH, Boles BR. Functional amyloids composed composed of amyloids Functional BR. AH, Boles n RE, Rickard a W ilm f SJ. An inflammatory polypeptide compl polypeptide inflammatory f An SJ. f f C, TH, Bach J, Sanchez KM, Crotty Al J, KM, Sanchez

serine metabolism of Stap 4533. [PubMed: 24082071] [PubMed: 4533. - ylococcus epidermidis, A athog. 2009; 5:e1000533. [PubMed: 19649313] athog.[PubMed: 5:e1000533. 2009; , Kline K, Nielsen H v E, Solin – h P o 1272. [PubMed: [PubMed: 1272.21169484] d ilms T f 200. [PubMed: 200.19710683] [PubMed: – arz S, Shore arz S, xtracellular polysaccharides are preeminent uropathogenic Escherichia uropathogenic polysaccharides are preeminent xtracellular – ylococcus epidermidis antimicrobial antimicrobial delta ylococcus epidermidis w e h ang R, Bach TH, Kretschmer D, Chen L, Kreiswirth BN, L, Kreiswirth Chen D, TH, Kretschmer R,ang Bach 975. [PubMed: 975.20086090] [PubMed:

W –

ano G, Ikuo M, Omae M, ano Omae Ikuo G, inograd :e8557. [PubMed: 20052280] :e8557. g soluble modulin in soluble modulin stap A, V - 1286. [PubMed: 22232686] 1286. [PubMed: B yCM, Klebano – Author manuscript; ed from Stap from ed e erdon J, Lacombe C, Crapart S, Héchard S, C, Héchard Crapart erdonLacombe J,

, Na rends Microbiol. 20 Microbiol. rends . v 78:963 KA, KA, V i Y T amasaki K, Sanchez KM, Dorschner RA, Lai amasaki Lai KM, Dorschner K, RA, Sanchez amasaki K, Muto

deaminase deaminase and D , Hiramatsu K, Sekimizu K. K, Sekimizu Hiramatsu , imbriae and and imbriae y Y Y - f amma) cooperates with host antimicrobial peptides to kill group A Streptococcus. kill A Streptococcus. peptides to group amma) with host cooperates antimicrobial e gulation promote bio T anger anger M, Sakinc , Khan , e g Jacques G, Jacques Sch mec on the mobile genetic element SCCmec r SCCmec genetic element the mobile mec on - w - - Y ylococcal hemolytic peptides. Peptides. 2011; 32:845 2011; Peptides. peptides. ylococcal hemolytic ell FR, Identi Otto DeLeo M. A, Peschel SJ, f e S, Engelmann I, Archambault M, Coleman DC, Coombs G Coombs M, DC, e Engelmann Coleman I, Archambault S, , Kim JE, Gallo RL. Select RL. Gallo JE, Kim , , Gallo RL. Stap Gallo , r f Mougeot FK, Buckles EL, Lockatell C Lockatell Buckles EL, FK, Mougeot h yticus. J Bacteriol. 2010; 192:4618 yticus. Bacteriol. 2010; J k athog. 2011; 7:e1001267. [PubMed: [PubMed: 21304931] athog. 7:e1001267. 2011; K - V V , Ito , ylococcus aureus from the urinary tract: association of isolation with symptomatic urinary symptomatic with ylococcus association isolation urinarytract: aureus of the from ylococcus aureus bio A, Otto M. The role of virulence determinants incommunity virulence determinants role of M. The Otto A, h serine artz K, Syed AK, Stephenso Syed artz K, P ype 1 Ber h h T ylococcus epidermidis: isolation and characterization. J Exp Med. 1999; Med.189:907 J 1999; Exp characterization. and ylococcus isolation epidermidis: - psm - B T w h ang R, Braughton KR, Kretschmer D, TH, S ang Queck Bach Braughton KR, R, Kretschmer phenol soluble modulins stabilizephenolmodulins Stap soluble 8:e1002744. [PubMed: 22685403] element M. Mobile genetic Deleo Otto FR, PLoS resistance MRSA. in Pelletie associated phenol [PubMed: 22251619] Stap Nizet Nizet dermodulins Dermatol. 2010;130:192 of stap Denham EL. Requirement of the agr locus for colo 193:1267 Bacteriol. 2011; Stap 2012; 109:1281 Nizet Nizet modulin One.PLoS 5 2010; orte ark S, Periasamy S, Joo HS, Duong S, Joo HS, Duong Periasamy Microbiol Spectr [PubMed: [PubMed: 17994102] Baba gene PLoS pathogenesis. Stap [PubMed: 10075974] of the structure and biological functions of a capsular polysaccharide produced by Stap saprop MS. 2 Microbiol. tract. Mol murine in the urinary coli virulence determinants [PubMed: 12180926] mediated r 2010; Immun. Klebano community for virulence determinants the D 81:4525 2013; Infect Immun. K P Bahrani W 106. Queck 106. S Queck 107. Monec JD, Brennen Rihs C, 108.RR, Muder 101. AL, Cogen A, 102. Marchand 103. Tsompanidou E, Sibbald MJ, Chleb 104. 105. Sch 97. Kaito C, Saito 97. Saito Kaito C, 98. Diep 99. Headl Mehlin C, 100. AL, Cogen 93. 94. 95. Anderson GG, Goller CC, Justice S, Hultgren SJ, Seed PC. Polysaccharide capsule and sialic acid 96. 92. wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

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A V 20. y age 32 – 101.

P - eillance 50. , and , v . Diabetes – acilities. y 19, a outelis outelis V c F - k ork at the associated associated - w yticus. A , S ork h ed in ed urinary depleted depleted gnan V - v w e omen. Am J ol

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- h diabetic diabetic patients. Eur J yelonephritis in yelonephritis - p 743. [PubMed: 23279021] . J Biol Chem. 2012; J Biol Chem. . ging pathogens. Am J Med. ging Am pathogens. – non y r e stap

v i A, Fridkin SK. National SK. A, Fridkin

Gonzalez Gonzalez wis AL. Urinary tract infection infection tract wis AL. Urinary at D - e g ylococcus saprop apastamopoulos apastamopoulos e h P elderly adult patients with urinary adult patients elderly focus on Stap focus n - el and cobalt in zinc and cobalt in el k ylococcus aureus isylococcusaureus i

h wis WG, L wis WG, , FitzGerald MG. Bacteraemia in diabetics. J in diabetics. ,MG. Bacteraemia FitzGerald e 153. [PubMed: 1753113] 153. [PubMed: y B. Risk of urinary tract infection and 2007. Infect Control Hosp Epidemiol. 2008; Epidemiol. Hosp Control 2007. Infect e care units in the United States. Crit Care Crit Care e the United States. in care units arez R, Pérez e W

– 1056. [PubMed: 8783709] 1056. [PubMed: . National Nosocomial Infections Sur . Nosocomial Infections National rte C, La Sorda M, Sanguinetti M, Juillard M, Sanguinetti M, rte C, La Sorda – v v ndiabetic ndiabetic postmenopausal i P . Coagulase – D to 1992; impact of pr diabetes, of 1992; impact to ert DM, Pollock ertPollock DM, onstantinou I, I, onstantinou A. Urinary tract infection in diabetic patients. diabetic infection in tract Urinary A. T Al 1260. [PubMed: 20662775] [PubMed: 1260. . The influence of diabetes mellitus on the on mellitus The.influence of diabetes

v k - – T e ni C, Sanguinetti M, Borezée M, ni Sanguinetti C,

69. [PubMed: 24416696] [PubMed: 69. apa igna igna – P

yticus. Eur J Clin Microbiol Infect Dis. 2012; 31:7 2012; yticus.Dis. Microbiol J Clin Infect Eur V h , Zhang L, Hao A, Cao X. Function of GRIM X. of Function Cao L, Hao , A, Zhang x I protein, in innate immunit x innate I in protein, e study between diabetic and , Burdon Burdon , P e v i artaglia artaglia ention, 2006 W 1991; 23:145 1991; resistant pathogens with associated healthcare pathogens resistant T - v articipating National Healthcare Net National Safety articipating Healthcare

ylococcal bacteremia. Clin Infect Dis. 2006; 42:46 2006; Dis. ylococcal Infect Clin bacteremia. R ailable in PMC 2016 June 01. e

y complications: opportunities, challenges, and a global call to a global call and ychallenges, opportunities, complications: P h transporter of Stap v - c a ylococcus epidermidis infections. Semin ylococcusImmunopathol. infections. Semin 2012; epidermidis , epidemiology and virulence of Enterococcus. Microbiolog Enterococcus. of and virulence epidemiology , y h er DH, Gaynes er R DH, Gaynes v eam, eam, gnan T e Bobillot A, BobillotMarti A, 564. [PubMed: 15746472] [PubMed: 564. Stap , Lepinski JL, , Lepinski JL, 19S. [PubMed: 12113867] 19S. [PubMed: . J Infect. J Infect. . - – P el ABC y – ylococcus aureus urinary tract infection: the role of undetected undetected the role of infection: urinary tract ylococcusaureus atel J, Horan TC, Si TC, atel Horan J, k h P , Hultgren S, Macones G, L S, Macones , Hultgren ork 219. [PubMed: 219.10743697] [PubMed: P A, Nuño FJ, Fernandez – ylococcus saprop utes to virulence. Mol Microbiol. 2013; Mol 87:730 2013; virulence. Microbiol. to utes w J 219. [PubMed: 3522748]

infections in medical intens infections h b – 892. [PubMed: 10362409] 892. [PubMed: alou E alou wn RM, Smyth wn RM, Smyth 287. [PubMed: 1341610] 287. [PubMed: – g o ards JR, Cul ards JR, – iström J, Sjöstedt A, Monsen iström J, Sjöstedt 1757. [PubMed: 19383684] 1757. [PubMed: w – ards JR, W Author manuscript;

. w 27235. [PubMed: 22665480] 27235. [PubMed: – , Ringertz O. Urinary tract infections caused caused by Stap infections tract Ringertz Urinary O. , Durant E. A E.nic Durant A entable cause pr entable of P 1011. [PubMed: 1011.18947320] [PubMed: - 214.22095240] [PubMed: A, Maradona v J – – , Lu H, Liu Q, Huang G, Lim C Huang H, Q, Liu Lu , e ylococcus aureus Opp1 ABC transporter imports nic imports ylococcus transporter aureus Opp1 ABC Y arlane IA, arlane Br o EJ, Fihn SD, Scholes D, Abraham L, Mons h F k y iderström M, o mellitus and bacteraemia: a comparat Med. 1:281 1992; Infect. 12:213 1986; Urol Int. 1999; 63:215 resistance in spectrumthe antimicrobial of and uropathogens 16545130] [PubMed: 6:54. Infect2006; Dis. tract BMC infection. 1A):14S 2002; 113(Suppl mitochondrial respiratory chain chain compl mitochondrial respiratory 287:27227 2009; 155:1749 System. Nosocomial Med. 27:887 1999; 1989 period the from Manitoba, during Canada, 1996; Dis. 22:1051 Infect Clin aboriginal origin. asymptomatic bacteriuria among diabetic and no 161:557 Epidemiol. 2005; the molecular epidemiology and clinical presentation, with a with and clinical presentation, theepidemiology molecular and Stap epidermidis [PubMed: 21533877] Healthcare Net Safety annual antimicrobial NHSN update: Net Safety Healthcare National to the reported of data annual infections:summary and Pr Centers Control Disease for 29:996 matchedcase control stud Johnson S. Stap Primary Johnson 29 1095 Dis. Clin Infect 2010; Microbiol Eur thetract. urinary J of hematogenous seeding as a pr 2:59 2013; Health Med. Glob action. Adv Borezée 2010; 77:1246 Mol Microbiol. tract infection. Stap conditions and contri 34:201 tract infection and subsequent and stap tract infection [PubMed: 16323090] Fisher K, Phillips C. The ecolog K, C. Phillips Fisher W Microbiol Spectr 123. Mac C, B, Longo 124. Meini M, Bonadio M, Gigli G, 125. Costarelli S, Bonadio M, Morelli and eme urinaryinfection:tract traditional Theetiology of 126. Ronald A. 118. Ed 119. MJ, Richards for acute LL. Hospitalization Friesen GK, Roos 120. Harding LE, Nicolle D, 121. B 122. Carton 114. 115.AI, Ed Hidron 116. Hedman 117. Chen 110. Gilbert NM, O’Brien NM, V 110.O’Brien Gilbert Delpo L, Remy M, Carrière 111.A, B, Hiron Posteraro Derré M, L, Carrière 112. Remy of 113.M. basis Otto Molecular 109. Baraboutis IG, Tsa 109. Baraboutis wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

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- aecalis. J Clin aecalis. I iv f ov Smith ON, ON, Smith . 2011; Infect Immun. 79:2901 - betic rats. Infect Immun. 1981; 34:773 1981; Infect Immun. rats. betic Felip M, S 3523. [PubMed: 3523.8751893] [PubMed: - F 4298. [PubMed: 18644886] 4298. [PubMed: g C, Gilmore MS, Johnson DE. Role of g Gilmore C, Johnson MS, – 2839. [PubMed: 19433548] 2839. [PubMed: r – – . A n . A aecalis OG1R T f A, Höök M, BE. A, Erlandsen Murray Höök SL, D

drug resistant enterococci: the of the the nature enterococci: drug resistant aecalis. aecalis. Infect Immun. 2004; 72:6032 - f vrich vrich H. Acute bacterial prostatitis: t A, Chuang a g Infect Dis. 1998; 4:239 1998; Dis. g Infect D r

M - aecalis OG1R aecalis a IG, a J, Huebner Sak IG, f , Sanguinetti M, ,Posteraro M, Sanguinetti B, v urinary tract infection. PLoS One. 2014; 9:e96295. One.9:e96295. 2014; infection. PLoS tract urinary ur A, Musquera

P ector results in attenuation of virulence and immunity in virulenceand immunity in of attenuation ector results a xtracellular matrix protein matrix protein xtracellular T v e - yelonephritis in dia ailable in PMC 2016 June 01. p aecalis. Infect Immun. 2013; 81:1696 Immun. aecalis. Infect vison ME. Experimental Candida albicans, Stap Candida albicans, Experimental ME. vison aecalis in urinary tract infection. PLoS One. 2014; 9:e107827. One. 2014; PLoS infection. aecalistract in urinary y are Eep bio and GM. AhrC v f e MM, Lindahl G, Gilmore Infection MS. Gilmore G, Lindahl MM, e e f

, Kling DE, Kasper DL. Group B Kasper Group DL. ,DE, Kling a n vious manipulation of the l of vious the manipulation k vicencio e a aecalis aecalis W , L 4372. [PubMed: 11401975] [PubMed: 4372. f P – ill

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- , Baghdayan AS, Drachenbe AS, Baghdayan , Carlemalm M, Lindahl G. Experimental Experimental M, Lindahl G. Carlemalm xpression in xpression Enterococcus V 200. [PubMed: 200.9864215] [PubMed: - , Gilmore Multiple MS. vison S vison e r alou J, Bujons – A. The etiology and management of acute prostatitis. Nat R acute A. of prostatitis. Themanagement and etiology F ilm

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actors in Enterococcus in Enterococcus actors gulates ace gulates , Riboulet , f , Baghdayan AS, Huyc Baghdayan AS, , e F gories according to a pr to according gories V A, Hung CS, Kline KA, Hultgren SJ. Streptozocin SJ. KA, Hultgren CS, Kline A, Hung occus occus e Rodríguez Rodríguez 212. [PubMed: 212.21403661] [PubMed: D ed in virulence. Infect Immun. 2009; 77:2832 2009; Immun. Infect ed in virulence. - e MM, Sahm D Sahm MM, e f LC, Michel JL, Gong E Michel Gong f JL, LC, bca, by a by bca, n – f v k cat - ol fel L, Pitsakis fel L, Pitsakis f v obser D, Ali L, Grohmann E, Huebner J, Sakinc E, Huebner J, obser D, Ali L, Grohmann , Giard ,JC. ace, Giard endolkar endolkar PM, Baghdayan AS, Gilmore MS, Shankar N. Enterococcal sur n virulence 23460519] Enterococcus pathogenesis of [PubMed: 24806450] of enterococcus lipoteichoic acid [PubMed: 25296179] bio and Endocarditis 17016560] 2807. [PubMed: enhances bio [PubMed: 15385507] adhesinace host to and collagen the by urinaryinfection Enterococcus tract [PubMed: 21505082] Y i (EtaRS) r 25385790] 395. [PubMed: HultgrenSchli SJ, gene, 1997; USA. Sci 94:13251 Acad group Proc B Natl Streptococcus. puri highly with encapsulated streptococcus, an bacterium, 1996; 64:3518 Immun. Infectproteins alpha. Rib and AcadUSA. Sci Natl Proc of protein. the alpha repeatC elements immunityof deletion tandem by 1996; 93:4131 Enteroc 69:4366 2001; Infect Immun. aureus, and Streptococcus aureus, and Streptococcus 6800956] 779. [PubMed: Orejas M, Baez sub 2006; 24:45 8:207 Eme future. agenda the for an problem and Enterococcus 1999; 67:193 Immun. urinary tract infection. Infect Immun. 2008; 76:4290 Immun. infection. urinaryInfect tract T W Microbiol Spectr 142. Diederich AK, 142. AK, Diederich 143. SR, Singh K 144. Nallapareddy 138. Nallapareddy SR, Singh K 138. Nallapareddy 139. Lebreton K 140.Singh Roh JH, Guiton AM, Manias Barnes PS, 141.KL, Frank 133. Li J, Kasper DL, Ausubel FM, Rosner B, Michel JL. Inact JL. Rosner Michel B, DL, Ausubel FM, 133. Kasper Li J, Stålhamma 134. C, Larsson 135. Mado Lockatell C 136. N, Shankar 137. 129. Millán Shos 130. Brede CM, 131. Huyc 132. Shankar 127. Rosen 127. Rosen 128. Ra wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

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aecalis to human platelets. Infect Immun. 2011; 79:2911 2011; Immun. Infect platelets. aecalisto human , Bertinetti O, Herbe O, , Bertinetti e ailable in PMC 2016 June 01. e 34. [PubMed: 22221809] 34. [PubMed:

f type pilus genes among Enterococci and demonstration of their F e12. v - – alaz K, Mee M, Mariscalco MM, Dun MM, alaz Mariscalco M, Mee K,

a , Caparon MG, Hultgren SJ. Mechanism for sortase localization for localization sortase Mechanism SJ. Caparon MG, Hultgren , – vidual su Ebp Pilus vidual P i er: , Monteal - W v y GM. D V i n

3247. [PubMed: [PubMed: 3247. erts i and – xploit int , Baudner , aecalis to aecalis e f ybo ybo S, Nielse F bv encoding genes, srtA and bps (srtC),to and bps bio genes, srtA encoding h - elopment. Infect Immun. 2009; 77:3626 2009; Infect Immun. elopment. manuscript; manuscript; A, Dun A,

ilm formation and urinary tract infection. PLoS One. 2013; One.8:e68813. PLoS 2013; infection. tract and ilm formation urinary t infection. Infect Immun. 2007; 75:5399 Immun. Infect infection. t v ation of Ebp ution of autolysin and Sortase a during Enterococcus Enterococcus a Sortase and during autolysin of ution , Nallapareddy SR, Murray BE. Relat BE. ,Murray Nallapareddy SR, f ution of ind of ution e D v b Lee J, Holland D, J, Lee Holland Mireles AL, Kau AL, Kline KA, Pinkner JS, NeiersJS, Pinkner AL,AL, Kline KA, Kau Mireles V b - - aecalis and its use in construction of a srtA mutant. Appl E of srtA mutant. Appl in construction a aecalisand use its f 5849. [PubMed: 16204495] [PubMed: 5849. Author aecalis su aecalis aecalis EbpA pilin mediates pilus function function in pilus mediates pilin EbpA aecalis ilm d ilm

– f f f . anek NN, anekJacques NN, el Med. 2012; Med.19:28 2012; el Caparon MG, Hultgren SJ. Pilin and sortase residues critical for endocarditis critical for and sortase residues Pilin SJ. Hultgren Caparon MG, v V ransl Med. 6 254ra127. 2014; ransl Normark B, Beatty B, Normark , Flores Neiers Pinkner GC, JS, Port ,Kline KA, PS, Guiton a athog. 2008; 4:e1000026. [PubMed: 18369475] athog. [PubMed: 2008; 4:e1000026. - r T V V 6075. [PubMed: 10531268] 6075. [PubMed: P T – 211. [PubMed: 19459002] 211. [PubMed: associated pilus biogenesis in Enterococcus in biogenesis Enterococcus pilus associated - 246. [PubMed: 246.20676385] [PubMed: – Mireles AL, Pinkner JS, Caparon MG, JS, AL, Pinkner Mireles brain barrier penetration. Nat Commun. 2011; [PubMed: 2:462. 21897373] 2011; Commun. Nat penetration. barrier brain yMalone H, - – - biogenesis, bio biogenesis, e ilm formation and virulence in a murine model of urinary tract infection. tract of urinary a model in and murine virulence ilm formation ilm f f inkle WB, Simon SI. inkleEnterococcus WB, Simon emp KD, Singh K emp KD, aecalis OG1RF sortase aecalis OG1RF Ferlenghi I. Pneumococcal pili are composed of proto are composed of pili Ferlenghi I. Pneumococcal A. PLoS bindingEnterococcus of Scimice. Enterococcus One. 2013; 8:e83637. [PubMed: 24363814] tract PLoS infection. W despite phago by human neutrophils 67:6067 bio 1:236 Murray BE. Conser Enterococcus roleof in adherence 21502588] 2920. [PubMed: l of the Cystic echinococcosis 2010). J Pili Doran Bacterial KS. blood Enterococcus Enterococcus e00177 infection. 2012; MBio. 3 in Enterococcus 2005; 71:5837 f trac model of urinary Murray BE. Contri pilus [PubMed: 23874774] ebp(fm) pilus of Characterization the Normark B, Normark bio [PubMed: 23913319] Henriques in e localization and sortase the role of 191:3237 Bacteriol. 2009; HultgrenContri SJ. dependent bio ion The SJ. metal B, Normark MG, Hultgren Caparon encoding Bee locus: a second pilus gene cluster in Enterococcus in genecluster pilus second encoding locus: Bee a 59:206 K Microbiol Spectr 158. Flores 159. Horsl 160.RM, Rakita 154. Nallapareddy SR, Sillanpää J, Mitchell J, Singh K T C, 155. S, Ewertsen Branci AS, Cutting EM, BJ, Kim Carmona A, 156. Banerjee Giusti M, 157. Hilleringmann 150. Kristich CJ, 150.Manias Kristich CJ, 151. K 152.Chang Singh Sillanpää J, C, Singh K 153.Nallapareddy SR, Sillanpää J, 146. Nielsen 146. Nielsen H J Rosch JS, Pinkner Kau SL, Lim A, AL, Chen 147. Kline KA, K Heuser J, E, AL, Hayes Dodson KA, Roth Kau Hung CS, R, Kline 148.PS, Guiton 149. Nielsen H 145. Schlüter S, Franz CM, Gesellchen Gesellchen S, Franz 145.CM, Schlüter wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

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k ascual ascual . 2008; . al inside al inside li , y P 677. - F iv , – 4874. r aecalis aecalis 1163. 1108. – f 1526. ypR in the the ypR in – – – Enterococcus Enterococcus h os A utes early to istance, and istance, b V ADH peroxidase, ADH 2006; 46:410 2006; al of gulates gulates erneuil N, Zhang X, erneuilZhang N, N e stress ande stress e stress sensing e stress e ract Infection Infection ract iv v v , Sanguinetti, M, V r oods VL J i i v TIR S. The Domain T - , Y

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aecalis into macrophages.aecalisinto J f

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K term permanent catheter catheter term permanent Y e A. Characterization of Ers, a a of Ers, e Characterization A. - iersin k e stress response,surv stress e ell RA, Ghosh S. A toll ell RA, Ghosh v v eith Surv JM. i W e peroxidases ( e Tchatalbach aecalis d a wski RR. Bladder histological histological wski RR. Bladder fray

f K , f o . J Urol. 1999; .161:1106 1999; J Urol. T aecalis in oxidat aecalis , Hart , r f Y aecalis. FEMS Microbiol Lett. Microbiol FEMS 2005; aecalis. . AsrR is an is oxidat AsrR . orld Journal of Gastroenterolog orld of Journal f orelli Le BrasR, orelli

V grate G, Reed JC, G, JC, grate Reed yFl C, T W

aart PS, PS, aart e e e A, Giard JC. Implication of Implication JC. e Giard A, fray fray g f k , Dmoch n ilm and planktonic Enterococcus Enterococcus planktonic ilm and yuria and infection in patients with patients indwelling in infection with yuria and f F a p al of Enterococcus al Enterococcus of P 357. [PubMed: 2713616] [PubMed: 357. – iv , Ammendolia MG, MG, , Ammendolia , Hart dependent MyD88 signaling contri MyD88 dependent P aecalis. Mol Microbiol. 66:1148 2007; Mol Microbiol. aecalis. - ola A Y

f k ytes in vitro. FEMS Immunol Med 2012; Microbiol. vitro.Immunol FEMS ytes in an den an c 3897. [PubMed: 3897.20566694] [PubMed: v 329. [PubMed: 329.18724530] [PubMed: fray – – f ysiological rolesthre ysiological of aecium peritonitis. J Immunol. 2008; 180:4865 2008; J Immunol. aecium peritonitis. . TLR2. h f intestinal Enterococcus intestinal Enterococcus aecalis. FEMS Immunol Med Microbiol. Immunol aecalis. FEMS , Santelli E, Le E, Le N Santelli , T aecium opportunistic traits, antimicrobial res aecium traits, opportunistic f aecalis Is Predominant among Urinary among Predominant aecalis Is

f T f ailable in PMC 2016 June 01.

v ant asion surv and a f v n e study of 761 patients. Arch Intern Med. 160:673 Intern 2000; patients. study Arch of e 761 Schweizer R, Pikis A,EstaySchweizer R, M, v i 1262. [PubMed: 15776371] 1262. - asthi S, Shankar N. Bio asthiShankar S, f – f w 21392. [PubMed: [PubMed: 21392.19535337] an der Poll an Poll der , Sanguinetti M, Posteraro B, Sanguinetti M, , B, Posteraro 16216443] illems RJ, Leclercq R, Cattoir Cattoir R, Leclercq illems RJ, , Li S, Liu Li S, Liu , – v A [PubMed: 10081848] [PubMed: erneuil N, Sanguinetti M, Sanguinetti Au N, erneuil W W e stress response response e of Enterococcus stress athog. 2012; 8:e1002834. [PubMed: 22876178] [PubMed: athog. 8:e1002834. 2012; e study of the the p e of study V

v v P gulates Host Inflammatory Response. Int J Microbiol. 2014; Microbiol.2014:918143. Response.2014; J Int gulatesInflammatory Host i i , Hammonds JC. Histological changes in the urinary bladder secondary to to bladder in thesecondary urinary JC. Hammonds changes , Histological e ageot N, Giard JC, Benachour A, Posteraro B, Au B, Posteraro A, Benachour Giardageot N, JC, T v

ents infection by uropathogenic bacteria. Science. 2004; 303:1522 2004; bacteria. Science. uropathogenic ents by infection , Hsu S Hsu , 1109. e illems RJ, Giebelen IA, v – Y k Schaik Schaik wnr e Author manuscript;

L

W Lek Cesk. 2008; Lek Cesk. 147:325 o . w WL, Lee YK. Lee YK. In w WL, e A, La Sorda M, Posteraro B, Laplace JM, Au Laplace JM, M, B, e La Sorda Posteraro A,

. PLoS PLoS . o an k y w gulator of Enterococcus of Enterococcus gulator v o e

A, Maki DG. The relationship between A, DG. The between relationship Maki , 141. [PubMed: 141. [PubMed: eeks CR, eeks Karkho P F ferent responses from host from phago responses ferent e r 282. [PubMed: 282.22333034] [PubMed: – f ydroperoxide reductase and Thiol peroxidase) in oxidat in Thiol peroxidase) and ydroperoxide reductase W k – -

h li e Comparat A. - k yl k w K, Baghdayan AS, w K, AS, Baghdayan gulator modulating Enterococcus Enterococcus gulator modulating ychl L, Zalud R. Changes in the urinary bladder caused by short by urinary caused in the bladder ychlChanges Zalud R. L, a erneuil N, Rincé A, Sanguinetti M, Au M, Rincé Sanguinetti A, erneuil N, e e aecalis in mouse peritoneal macrophages. Infect Immun. 1999; 67:2160 Immun. Infect macrophages. aecalisin peritoneal mouse ambyah ambyah 65:270 of Enterococcus Containing Locus Isolatesand D [PubMed: 25147569] J Biol domain. TIR bacterial a structure crystal of immunity: in innateJ. mimicry Molecular Chem. 284:21386 2009; in cell lines. human intestinal inflammatory responses 7:017. [PubMed: [PubMed: 18354210] 63:354 Br 1989; J Urol. catheterisation. urethral insertion. Cas urinarycathete indwelling chronic changeswith associated discussion 1108 urinarycatheters: prospect a [PubMed: 10724053] elicit di PrfA [PubMed: 16553815] virulenceand oxidat 252:137 Enterococcus A andof B reductases methionine sulfoxide 2010; 78:3889 Immun. virulence. Infect that pr receptor [PubMed: 15001781] Florquin MJ, S, Bonten murine Enterococcus host defense in Glycosaminoglycans mediate i Glycosaminoglycans mediate 191:1253 Infect Dis. 2005; Hart Al Enterococcus of virulence macrophages and [PubMed: 17971082] GiardDhalluin A, JC, r pathogenicit f 10225869] T V Microbiol Spectr 175. Kraemer TD, Quintanar Haro OD, Domann E, Chakraborty E, Chakraborty OD, Domann 175.TD, Quintanar Haro Kraemer 176. L SL, Chan LHM, Ch 177. Ng 170. Goble NM, Clar170. NM, Goble 171. P H, Goldman Juk WH, Stonehill 172. Delnay KM, 173. 174. D 166. 167. Hart Zhao C, MB, Buss Greenblatt MS, Hayden 168. Zhang G, Zhang D, M, 169. Leendertse 162. Baldassarri L, Bertuccini L, Creti R, Filippini Filippini Creti R, L, L, Bertuccini 162. Baldassarri S, 163. Sau La Carbona 164. Lebreton E, Riboulet 165.JC, Giard 161. Gentry wis e Kline and L

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– enger JD, Stephens DS. A population DS. enger JD, Stephens W ays. PLoS One. 2014; One.9:e97523. 2014; PLoS ays. . Management of urinary tract infections infections tract of .urinary Management orld J Gastroenterol. , gnan gnan W gnan T w F e e

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e o R, Lazer o Lazer R, actor for ad actor for ailable in PMC 2016 June 01. , Xiao M, , M, Xiao vision of Bacterial Diseases, National Center National Diseases, for Bacterial of vision 134. [PubMed: 1744182] 134. [PubMed: f i k v F – a . 2001; .34:153 2001; r gers EA, Dörr PJ. Morbidity related to maternal group B relatedgroup to maternal MorbidityPJ. gersDörr EA, 1986. [PubMed: 22530608] [PubMed: 1986. , Smith JD, Schuchat , A, JD, Smith e – T gien , Jacque B, Menard J ,Menard Jacque B, e5. [PubMed: [PubMed: 17547879] e5. r , Theunissen C, Pepersack , Pepersack C, Theunissen P – eriat e disease due to group B e group to disease due

F 2060. [PubMed: [PubMed: 19439533] 2060. , Zhuo , v

yelonephritis: unresol r i – . J Med Microbiol. 1998; 47:649 1998; Microbiol. Med J . 990. [PubMed: 990. 17002033] , Se , p y , Bunchoo M, Nuntachit N, Sirisanthana N, Nuntachit , M, Bunchoo 128, 133 128, 1811. [PubMed: 1811.8502269] [PubMed: 582. [PubMed: 582.2927852] [PubMed: – as Y 70. [PubMed: 70.12601337] [PubMed: – – – v W A – n

w WL, Lee YK. YK. In Lee w WL,

et o k y RC, Stull ogelSte PM, alactiae in adults at Chiang Mai Un Mai inadults at Chiang alactiae mhan HN, Simons KM, KM, Simons HN, mhan v illiams MA, Kass EH. Pr MA, Kass illiams , Bullen M. Bacteriuria in Pr , M. in Bullen Bacteriuria ve g Author manuscript; P

122. 125 122. . W am A, Benoit eintraub – . Z Gerontol G Z . g y r W Epidemiology of urinary tract infections: morbidit incidence, infections: urinarytract Epidemiologyof

Smith Smith . Antibiotics for asymptomatic bacteriuria in pr in bacteriuria asymptomatic .for Antibiotics pr in bacteriuria asymptomatic .for Antibiotics - , Kasper DL. Group B streptococcus infection in mother and child. Hosp Pract (O Hosp mother child. and in infection B streptococcus Group ,DL. Kasper B streptococcus: is it a risk is risk it a B streptococcus: F F F arith R, arith Julla - y Har MM, an R, Nicolle LE, McGlone A, Hooton TM. Asymptomatic TM. Hooton Nicolle McGlone A, an LE, R, w ersity of group B streptococcus serotypes causing urinary tract infection in urinaryadults. infection J Clin serotypestract causing B ersity streptococcus group of alle C, Martin E, Martel MartinE, Martel alle C, e g ysician. 74:985 2006; v yer I, Me i iv ang S, Hibberd ML, Pettersson S, Lee YK. Enterococcus S, Lee YK. Enterococcus Pettersson ML, ang Hibberd S, ang S, Ng LH, ang LH, Ch Ng S, h yelonephritis. Urol Clin North Am. 2008; Am. 35:1 yelonephritis.Urol North Clin R, essous e erani JR, McGee L, Schrag SJ. D SJ. McGee L, Schrag erani JR, r arl oxman oxman B. 2001; 2:CD000490. [PubMed: 11405965] 2001; [PubMed: 2:CD000490. 10796206] 2000; [PubMed: 2:CD000490. Dis. 14:927 Infect 1992; asymptomatic Clin bacteriuria. associated with 1533541] relationshipasymptomatic between 73:576 Gynecol. 1989; Disease for Immunization Respiratory Centers Diseases, and p 17999886] 507. [PubMed: pr in early streptococcal bacteriuria 196:524,e1 Gynecol. 2007; group 25:1983 Neonatal 2012; Med. P 14238090] bacteraemia in the bacteraemia the elderl in i basedof assessment J Med.328:1807 1993; a Streptococcus 21612629] [PubMed: 11:149. Infect Dis. 2011; Scand. 85:1027 2006; Gynecol Acta Obstet streptococcal infections. 18:525 1986; Dis. J Infect Scand colonization. neonatal risk for countin increases urine [PubMed: 3544201] modulates inflammation through MAPK signaling path MAPK through modulates inflammation [PubMed: 24830946] 49:53 Dis Mon. 2003; elderl in the 1991; 26:111 D Microbiol.47:2055 2009; inflammatory responses cell in lines. human intestinal inflammatory responses 18286689] 1076. [PubMed: V K F L, Bjerre Elfström Polbe B, K, Persson W F T W Microbiol Spectr

195. Smaill 196. Smaill R, 197. Mittendorf Hobbins JC, Brac M, M, Sirtori Oyarzun E, Mazor 198. R, Romero 199. 190. Nicolle LE. Complicated Complicated 190. LE. Nicolle 191. Anderson BL, Si 192. 193. Col 194. Kincaid 185. 186. Chai Oost 187. Muller AE, 188. urinarytract Uncomplicated 189. LE. Nicolle 179. 180. 181. B 182. R Haft J 183. KB, WH Ulett Benjamin 184. 178. wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

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y es binding of GBS to bladder es uroepit to bindingGBS bladder of 1112. [PubMed: 14999615] 1112. [PubMed: e accines: the group B streptococcus paradigm. paradigm. J B streptococcus accines: the group v – v y outcomes in y outcomes ol wl Sweih Sweih N, Rash c v o - n 254. [PubMed: 17464804] [PubMed: 254. 36. [PubMed: 21088663] 36. [PubMed: eillance samples for the detection of GBS detection for the eillance samples – ances in understanding the molecular basis of group B of group basis molecular the understanding ances in – v er CJ. Use of type V group B streptococcal conju streptococcal V group B CJ. type er Use of v accine in healt in accine based based gnan k - v e ards MS. Dose inflammation inflammation aoletti LC, Kasper DL, Ed DL, aoletti Kasper LC, 10):1 w ate - P ang A, Amaral FE, Ratner Amaral Ratner AJ. β FE, ang A, Infect Dis. 2004; 190:558 2004; Dis. Infect g v Mol Med. 2008; 10:e27. [PubMed: 18803886] 10:e27. 2008; Med. v Mol wide mapping of wide mapping ailable in PMC 2016 W - e v resoldi E, Berardi A, Creti R, Ba Creti R, A, resoldi E, Berardi a tetanus toxoidconju tetanus . Immunization .of pr Immunization streptococcal disease streptococcal - T 152. [PubMed: 20300409] [PubMed: 152. P ies a unique bladder transcriptome that that signi a transcriptome ies unique bladder mothers and their in their and mothers . Recent ad Recent . – f V , Lindblad M, Fredriksson M, ,M, Fredriksson Lindblad ards MS, Ba ebb Cr RI, D, Ipe Y 115. [PubMed: 19086816] [PubMed: 115. w ic induction of interleukin 1alpha. J Infect Dis. 2010; Dis. 201:866 2010; 1alpha. J Infect of interleukin ic induction

W ferent group B streptococcal type V capsular polysaccharide V type B streptococcal group ferent 210. [PubMed: 210. 19912341] f 73. [PubMed: 73. 12825173] – f 3368. [PubMed: 3368.11348699] [PubMed: ani M, ainst urinary tract infection. Infect Immun. 2012; 80:3145 2012; Immun. Infect infection. urinary tract ainst – ferent types types of sur ferent conju alent B streptococcal group – f – aolettiEd LC, g v g 2 ang ang i a P Infect Dis. 2004; 189:1103 Dis. Infect Y

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P speci , – - T Shemmari M, Thalib L, Al Thalib L, Shemmari M, - tetanus toxoidconju tetanus Author manuscript; -

ic mucosal and systemic immune responses in mice. FEMS Immunol Med FEMS in mice. responses immune systemic mucosal and ic . gård f y X, Cui AJ, r omen to 2 di to 2 omen ut GBS ut e ebb RI, Ulett KB, Cui X, Benjamin WH, WH, Cr KB, ebb Benjamin Cui RI, X, Ulett accines. accines. J aoletti LC, Rench MA, Guttormsen Ed MA, Guttormsen HK, aoletti LC, Rench b w v P W u L, Li S, Shen X. Intranasal immunization with GBS sur GBS L,X. Intranasal with Li S, u immunization Shen y h Y ate g y HC, Doran KS, Nizet Doran yNizet KS, HC, xisting immunity for systemic and mucosal immune responses to intranasal immunization immunization to intranasal responses immune mucosal and immunityfor xisting systemic arit I, Rinaudo CD, Galeotti CL, Maione D, Ghezzo C, Buttazzoni E, Rosini Runci R, Buttazzoni E, Rosini Ghezzo Maione C, D, CL, RinaudoGaleotti arit CD, I, enting bacterial infections with with pilus infections enting bacterial ention of perinatal group entionB perinatal group of e e g er CJ, CJ, er M, RenchFernandez MA, CJ, er RenchMcInnes MA, CJ, er er CJ, Rench MA, Rench MA, CJ, er v v - r k k k k e e eng, CKK.; Sheng, X.; Byington, C. Pr C. eng, CKK.;Byington, X.; Sheng, accine. 19:3360 2001; ulkarni R, Randis TM, Antala S, TM, ulkarni RandisAntala R, 27:252 2007; aginosis. J Obstet Gynaecol. accine in adults 65 accine in an CK, Car CK, an alazzi DL, Rench MA, Ed MA, Rench alazzi DL, and potent [PubMed: 20132033] host Group B Streptococcus enhances 23505569] [PubMed: 8:e59091. 2013; urinaryinfection. One. tractPLoS J Glob 2009; Infect Dis. 1:151 v with group B Streptococcus type III capsular type polysaccharide with Streptococcus group B V induces speci Microbiol.58:20 2010; Expert R Streptococcus virulence. Ulett GC. Schembri Genome MA, in identi mice Escherichia coli antimicrobial defense a [PubMed: 22733575] i infection urinary Streptococcus tract (GBS) v of healt conju of immunogenicity a b 188 Infect Dis. 2003; polysaccharide type capsular III [PubMed: 12850362] pre Streptococcal bacteriuria. Annual Meeting of the Pediatric the Meeting of Annual Streptococcal bacteriuria. Canada. 2010. between Comparison di parturient both colonization in 14614254] 230. [PubMed: S, Mora M, Buccato Pr 199:108 Infect Dis. 2009; polysaccharide [PubMed: 16919857] Pr Recomm Rep.59(RR MMWR 2010; K T P W Microbiol Spectr 201. Hammoud MS, Al MS, 201. Hammoud 214. Sumati AH, Saritha NK. Association of urinary tract infection in infection tract Associationurinary AH, Saritha of NK. 214. Sumati 213. in pr Shakiba M. Afrakhteh infections SH, tract M, 215.Urinary Sharami 209. Xue 209.G, Xue 210. Mais 211. 212. GC, Ulett 204. 205. Ba 206. Ba 207. Ba X, Lage 208. Shen 202. Ma 203. Ba 200. wis e Kline and L

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e v aginalis. J Biol aginalis. v 3447. [PubMed: yder HC, yder HC, – e 765. [PubMed: 1731. [PubMed: 917. [PubMed: 576. [PubMed: 8841221] aginosis is impr aginosis – – – – v

256. [PubMed: 2915019] 256. [PubMed: – aginosis in a murine model of aginosis a model in murine . Pediatr Infect Dis J. Pediatr Infect2008; Dis . v Smith K, Smith Critchl - y alidity of the of alidity the gradation, foraging, and gradation, and foraging, S621. [PubMed: 25414415] S621. [PubMed: o 550. [PubMed: 21895858] [PubMed: 550. V e ention of recurrent urinary tract ention of urinary recurrent

– – ystitis. Epidemiol ystitis. Zh Mikrobiol v c e g SC, Cappello M. Acute Acute M. SC, Cappello g oung r old b old Y - controlled phase 2 trial of a of trial phase 2 controlled xual transmission. J Exp 1991; Med. xual transmission. r - e

, Bruun B,, Schønh Bruun al M. Urinary tract infections ininfections tractpr alUrinary M. yea f SJ, SJ, f W iol. 1991; 29:1730 iol. 1991; Aerococcus sanguinicola infection: clinical clinical infection: Aerococcus sanguinicola - f wis AL. D wis AL.

761. [PubMed: 25439274] 761. [PubMed:

e lw –

A, Sweet RL. A, RL. Sweet producing Lactobacillus species in normal species in Lactobacillus producing J

- er BR, Kaur A, Landay AL, Spear A, er Kaur Landay G AL, BR, ent infection by pathogenic bacteria. Microbes bacteria. pathogenic entby infection ader R, Carpenter JL. Clinical signi aginally for aginally pr k v F v e gor a eenendaal D. Aerococcus urinae: eenendaal Aerococcus s urinae: D. . Diagn Microbiol Infect Dis. 2005; 53:289 1217. [PubMed: 21498386] 1217. [PubMed: e V , Khande , – w , V e fect of Lactobacillus acidophilus on human acidophilus on human of fect Lactobacillus f W vi ferson KK, Buck GA. The changing landscape of the the of Thechanging landscape ferson KK, GA. Buck adapted Actinobacterium Gardnerella Gardnerella Actinobacterium adapted e e f en intr - aginalis. PLoS One. 2013; 8:e59539. [PubMed: 23527214] [PubMed: One.8:e59539. 2013; PLoS aginalis. R xually transmitted infections that may influence transmission transmission influence that may infections transmitted xually v ailable in PMC 2016 June 01. e v

i v e r a, LI.; Gudima, IA.; Miroshnichenki, EA.; Ibish EA.; Miroshnichenki, IA.; LI.; Gudima, a, aard Sönksen U C, , Je a Am J Obstet Gynecol. 2002; J Obstet 186:916 Gynecol. 2002; Am v

ondo S, Linnan M. Reproducibility of a scoring system for gram for system gram a of ondo scoring S, Reproducibility Linnan M. g P i r ev illiams Klebano BL, nd s agina elstein R, Hampton L, Edbe elstein Hampton R, w 88:573 1996; aginosis. Obstet Gynecol. omen with chronic recurrent recurrent chronic omen with ard MR, ardHama MR, 40:761 2008; Dis. ication. J Infect Scand v k iricidal iricidal f v f W ydrogen peroxide w aginosis. Microb aginosis. J Clin f asil aginosis. J Clin Microbiol. 1989; 27:251 1989; Microbiol. J Clin aginosis. V h v wis AL. Clinical features of bacterial wis AL. featuresbacterial of Clinical v . V e 12079. [PubMed: [PubMed: 12079.23479734] 195. [PubMed: 195.21143335] [PubMed: 12. [PubMed: 21446162] [PubMed: 12. W – – aginosis. C, Rasmussen M. Clinical and microbiological features of bacteraemia of features bacteraemia M. microbiological Clinical and C, Rasmussen – R v . J Infect Dis. 3):S616 2014; . 210(Suppl J Infect A atkins K, Jinadatha C,

MI.; MI.; V 324. [PubMed: 11909742] 324. [PubMed: vick PR, vick PR, eung M, Hooton TM, Fredricks DN, Roberts PL, Czaja CA, CA, PL, Czaja Roberts DN, Fredricks Hooton TM, M, eung W ouw R, ten ouw R, ten Kate – w KL, Fin w KL, a k e Y alence alence of an, an, s WG, L s WG, y virus type 1: possible role in heteros y possible role in 1: type virus - g c ev Author manuscript; o wi

g Jensen K, Oste g Jensen K, . e r A, D ed infection in ed infection 4:319 K Cox M, Stamm placebo WE. M, Randomized, Stamm Cox infections and endocarditis. J Clin Microbiol. 2010; 48:3445 2010; Microbiol. and endocarditis. J Clin infections x , Zari Gilbert D, D , aginal microbiota a aginal microbiota icien Petersson , Soete P

f T ritis caused by Aerococcus urinae in a 12 in urinae caused ritis by Aerococcus , Krohn MA, Hillier SL. Reliability of diagnosing bacterial bacterial of diagnosing Reliability Krohn MA, ,SL. Hillier fman fman M, V F

292. [PubMed: 292.1647436] [PubMed: f rube P f SJ, Coombs Coombs SJ, f e JR, Hillier SL, Sobel JD, McGr Sobel SL, JR, JD, e Hillier 762. [PubMed: 762.18574434] [PubMed: – f T k associated HI associated – - Ho omen bacterial omen with - ance and bacterial identi bacterial and ance w gis R, Andresen K, Christensen JJ. Six cases of cases Six gis R,JJ. K, Andresen Christensen r ev wis WG, Robinson LS, Gilbert NM, Perry JC, L NM, Perry Robinson LS, Gilbert wis WG, omen omen with bacterial , Fiedler yeloneph aginal infection with Gardnerella with infection aginalGardnerella aginal microbiome. Clin Lab Med. 2014; 34:747 2014; Lab Med. Clin aginal microbiome. e with Aerococcus urinae. Clin Microbiol Infect. 2012; 18:546 Infect. 2012; Microbiol urinae. Clin with Aerococcus p 27:760 Da rel 19086249] bloodstream 20660216] and immunode 174:289 J Reprod Am genital tract. in the female responses immune innate on of bacteria commensal 2011; 65:190 Immunol. Infect. 2002; Aerococcus urinae: a retrospect [PubMed: 16269223] v of the sialoglycans mucus by Chem. 288:12067 2013; Y g crispatus probiotic Lactobacillus 52:1212 Dis. infection. Infect Clin 2011; Bacterial mi 2011; Immunobiol. 1:8 KK. Pr Holmes v of cell J Clin29:297 1991; Microbiol. stain interpretation. of gram method standardized 1706728] bacterial stain of diagnosis 1722221] for of the diagnosis bacterial w 12015512] Microbiol Spectr 232. Murray TS, Muldr 232.TS, Murray 233. Ibler K, 234. Jong M de 227. Klebano 228. Mirmonsef pr to Lactobacillus Use of J. 229. Burton Reid G, 230. Sierra 231. E, Senneby 223. L Au 224.AE, Stapleton IuL; 225. Naboka, 226. Eschenbach 217. Huang B, Fettweis JM, Brooks J Brooks JM, Fettweis B, 217. Huang 218. RA. Cone 219. R Nugent Josodi SL, 220.MR, Hillier Joesoef 221. Schweb NM, 222. L Gilbert 216. Hillebrand L, Harmanli OH, Whiteman Whiteman L, 216. OH, Harmanli Hillebrand wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

573. 573. 643. 643. 447. 447. – age 39 – –

P

ierarztl ierarztl

760. 760. T – . y ainst ainst p g o frequently o frequently

yelitis, yelitisin w p p . 2004; 64:569 2004; .

y ystosco c results of a of results . 1999; 111:446 . 1999; r - atal endocarditis f y transplant recipients: ytransplant recipients: 721. [PubMed: 1815334] 721. [PubMed: e enteen cases. Clin Infect Clin enteen cases. – G. Urinary tract infections infections tract Urinary G. v ystitis and ystitis e c A [PubMed: 2723037] [PubMed: an unnoticed urinary tract an tract unnoticed urinary e32. [PubMed: 22386439] e32. [PubMed: iaurre N, Muñoz Bellido JL, N, iaurre iedermann CJ. Septicaemia CJ. iedermann Septicaemia ication suis of ication Actinomyces f wer antibiotics a wer antibiotics – f -- . Eur J Clin Microbiol Infect Microbiol Infect Clin Eur . J e W ochensch w e coccal and coccobacillary and coccobacillary coccal e e 730. 730.

W v 780. [PubMed: 20482457] [PubMed: 780. – . 2003; [PubMed: 61:463. 2003; . i vi

– y e anism . Bacteremia caused by multiply . caused by multiply Bacteremia

g reclassi F

orner B. Danish ALO Study ornerGroup. Danish B. r . Corynebacterium suis infectionin Corynebacterium . vity of n of vity Eur J Clin Microbiol Infect Dis. 1997; Dis. Microbiol Clin Infect Eur J posit K i - 830. [PubMed: 830.18260786] [PubMed: . and description of Actinobaculum Actinobaculum and .of description e o W v – k ien Klin ien Klin o li . 2012; 79:e31. - v R, v R, W 903. [PubMed: 9226926] 903. [PubMed: . n eatures of Eubacterium suis. Microbiol. EubacteriumJ Clin suis. eatures of ahn y y dysfunctionand graft o ere consequences. Urolog anisms: reportanisms: of s b – h k Andrés A, San Juan R, Lizasoain M, Aguado Aguado M, San Juan Lizasoain R, Andrés A, v , Soriano g lw r e F , Collins MD. Characterization of , MD. Characterization some Collins Aerococcus urinae in urinary tract infections. infections. J tract in urinae urinary Aerococcus P

e o orner B. Urosepticemia and orner Urosepticemia B.

k K li A. In vitro act A. In

- J e uropat e ication of gram ication of v f g G, Bol i

r agüe Guirao G, GuiraoGutiérrez Zu G, agüe os MC, Janssens MM, Buiting MM, Janssens os MC, . Mortality from grossly encrusted bilateral . Mortality grosslyencrusted from bilateral ystitis. ystitis. Urolog Y 496. [PubMed: 14602367] 496. [PubMed: V F c andamme andamme – ailable in PMC 2016 June 01. 8645844] V v 546. [PubMed: 2736106] 546. [PubMed:

icum: six case reports and six case reports r icum: a Møller A, – aard aard H. Aerococcus - 1705. [PubMed: 10747177] [PubMed: 1705. g o M, Morales JM, JM, M, Morales o – Infect Dis. 2008; Dis. 46:825 2008; Infect , Amtsbe r anisms. Scand Dis. 23:717 J Infect anisms. 1991; . Aerococcus urinae and Aerococcus sanguinicola, t Aerococcus sanguinicola, . and Aerococcus urinae F g av P all all E, r v aerk J, Kristensen B,aerk Kristensen S J, onnell onnell W Br F - e o e er . Clin Clin . , genomics as the Rosetta Stone. Clin Microbiol Infect. 2008; 14:632 2008; Infect. Stone. Microbiol asClin the Rosetta genomics k k y P li grand grand eium, Corynebacterium amycolatum and Corynebacterium urealyticum. Int Int urealyticum. Corynebacterium and amycolatum Corynebacterium eium, -

e k 357. [PubMed: 2219105] 357. [PubMed:

517. [PubMed: 11561814] 517. [PubMed: 947. [PubMed: 947. [PubMed: – , Gallo RL. Skin microbiota: a source of disease or defence? Br J Dermatol. defence?of source Br a disease or J microbiota: RL. Skin Gallo , – – , García V orner Kjae B, e isolates from human human clinical e from specimens: isolates F 455. [PubMed: 18275522] [PubMed: 455. k ystitis by Corynebacterium group D2. group Urolog ystitisCorynebacterium by . Int J Syst Bacteriol. 1997; 47:899 Int Bacteriol. J Syst . Author manuscript; K

901. [PubMed: 6808018] [PubMed: 901. – c v . li aryan M, Haddad E, Dore B, Lottmann HB. LottmannEncrusted HB. B, aryan E, Dore Haddad M, vies BJ, viesO’D BJ, alsenE, A – - oh C, Attorri S, Clarridge JE III. III. JE oh Clarridge C, Attorri S, resistant bacteria. J Clin 1989; 27:724 J Microbiol. bacteria. resistant o a g - F r obal L A, w

Natal I, Guerra J, Alcoba M, Cachón Cachón Alcoba M, Natal I, Guerra J, e cohort stud ied uropathogens. Scand J Infect Dis. 2010; 42:775 J Infect Scand ied uropathogens. Dis. - K , D , Nagl M, Hausdorfer J, Gschwendtner A, Pechlaner C, C, Pechlaner A, Nagl Hausdorfer Gschwendtner M, J, , f v A, A, , Rauch A. Microbiological and clinical features of Corynebacterium urealyticum: Corynebacterium clinical Rauchand of , Microbiological features A. , i 875. [PubMed: 875.9495666] [PubMed: Y P F W , Ma , V – Medrano Medrano P - via Hernández M, García Rodríguez viaRodríguez García Hernández M, o ldren: an unusual condition with s an ldren: condition potentially unusual gienek J, Reddy CA. Nutritional and metabolic f and metabolic gienek Nutritional J, CA. Reddy g wson wson e Kaup Liebhold M, endt M, e ancomycin a acklam R, Hollis D, Collins MD. MD. Identi R, Hollisacklam Collins D, resistant corynebacterium urealyt resistant corynebacterium Dis. 2001; 20:514 Actinomyces com suis (Soltysand as Actinobaculum Spratling) schaaliin sp. 1982; 15:895 of and specialurine studies consideration with diagnosis swine.Clinical 1. Prax. 18:353 1990; chi [PubMed: 15351595] kidn urealyticum in Corynebacterium to due infection tract UrinaryJM. for an etiology obstruct underdiagnosed prospect S jei Corynebacterium 22:492 J Antimicrob 2003; Agents. [PubMed: [PubMed: 7747103] Aerococcus urinae. by caused and endomyocarditis [PubMed: 10420497] urinary tractand stones [PubMed: 18558935] 2008; 158:442 ureteritis, and 12597981] causedaerococcus by 1989; pathogen.97:539 APMIS. v misidenti Clin 2000; 38:1703 Microbiol. The Netherlands. of urinae in the south with Aerococcus 16:871 Bacteremia/septicemia due to Bacteremia/septicemia Aerococcus due Dis. 1995; 21:943 W W F Microbiol Spectr 252. L 253. 254. 247. Meria Encrusted SA. 248.MH, Strope Johnson 249. López Peris B, J, 250. Hernández Mora Sánchez 251. Fernández 242. Heilesen AM. Septicaemia due to Aerococcus urinae. Scand J Infect Dis. 1994; 26:759 J Infect 1994; Dis. urinae. Scand due Aerococcus 242.AM. Septicaemia to Heilesen 243. Gritsch 244. Soriano Nizet 245. AL, Cogen 246. Chung S 236. Christensen JJ, Gutschik E, Friis E, Gutschik JJ, 236. Christensen JJ, 237. Christensen 238. 239. Cattoir 240. K Zhang Q, L, Sabbe ME, Kasteren 241.PM, Schuur 235. Christensen JJ, Jensen JJ, I 235. Christensen wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

w

– e - 285. 285. age 40

– ere ere

2371. Dis. P v

– 410.

orkin, –

w

ierarztl Prax. ierarztl T an De an Vy De 1031. [PubMed: 1031. . V r – . BMC Infect BMC . 267. [PubMed: 69. [PubMed: 69. y – – 80. [PubMed: 80. an Furth an Furth AM. – v alence of Actinobaculum Actinobaculum of alence , 1173. [PubMed: – yelonephritis of yelonephritisswine of W ev p 3569. [PubMed: 16000509] 3569. [PubMed: . Actinobaculum schaalii ging Uropathogen? Case Rep ging Case Uropathogen? – F yeloureteral junction Actinobaculum urinale from a urinale from Actinobaculum r

p ational stud ational 2011; 17:1027 2011; v

. 2004; .111:67 2004; r 440. [PubMed: 12811591] [PubMed: 440. e234. [PubMed: [PubMed: 22211919] e234. García G. Actinobaculum schaalii schaalii G. García Actinobaculum – – idmer A idmer

292. [PubMed: 292. 6010034] - ystitis and ystitis and , Camps K, Celens A, , Camps – Prax. 1987; 15:263 1987; Prax. c e obser e 506. [PubMed: 506.22749060] [PubMed: W P yo v – i endtM. The pr o ebrandt, E., editors. The Prokaryotes. N editors. The Prokaryotes. ebrandt, E., ging uropathogen. J Infect. 2012; 64:260 ging 2012; J Infect. uropathogen. os k W r aribaculum, and Mobiluncus. In: D aribaculum,In: Mobiluncus. and V ochensch in a child with with in a child V a M, Ronald A. First report of Actinobaculum A. First report a of Ronald M, ger D, ger D, ierarztl ierarztl angrene. J Clin Microbiol. 2011; 49:2369 J 2011; angrene. Microbiol. Clin g Infect Dis. 2010; 16:76 g 2010; Infect Dis. W r f amily Actinomycetaceae: The The Genera amily Actinomycetaceae: eme r T g grist HH, Jaton K, Lienhard R. Actinobaculum R.grist K, Lienhard Actinobaculum HH, Jaton F gion (Russian Federation) by indirect indirect gion by (Russian Federation) e m schaalii: An Eme schaalii: An m an den Hoek J, Hack an W Hoek den . Corynebacterium suis infections in infections swine. 2. suis . Corynebacterium 12; 101:e232 12; e v H.; Stac H.; - ws. ws. W onine D, g Infect Dis. 2010; g 16:1171 Infect o r García M, García R . 20 . r K - r ierarztl ierarztl , K , et J. 1966; 7:291 et1966; J.

w of an w of r T e

V ournier’s J, Prag J. Actinobaculum schaalii: a common cause of vi g G, F

oul PH, e r ailable in PMC 2016 June 01. , Ruiz k aediat 537. v P P

- a ritten ML, Si ML, ritten el 47. [PubMed: 19883165] 47. [PubMed: , Zarfel G, Salzer HJ, Krause R, Grisold AJ. Endocarditis caused caused Endocarditis R,AJ. Grisold G, HJ, Krause Zarfel , Salzer v – T T Arcanobacterium, Arcanobacterium, a ebrandt, E. The E. The ebrandt, k eisser eisser M, Goldenbe ailure. J Clin Microbiol. 2005; J Clin 43:3567 2005; ailure. Microbiol.

W García García , Amtsbe , f - g, E.; Schleife g, E.; r endt M, Dromme W alentin alentin arca A, arca ation of 20 cases. Clin Microbiol Infect. Microbiol Clin cases. 20 ation of .; Stac rappen S, Cleenwerck I, De rappen S, ystitis in breeding in s ystitis breeding v V W V F

T c time polymerase chain reaction. Scand J Urol Nephrol. 2011; Nephrol. 45:406 2011; J Urol Scand reaction. chain polymerase time Smit AM, S an - d KA, Manickam K, Ng B, Al K, Manickam d KA, - e HL, Soltys MA. A case of infectious infectious of e case HL, Soltys MA. A V indings in the urinary tract with special reference to the to the bladde reference special with urinary tract in the indings k f Author manuscript;

599. [PubMed: 2080504] [PubMed: 599. , Leibold Leibold , . assin, A assin, – aterson R, Grant aterson J. Grant Actinobaculu R, V Y P , S.; Rosenbe , S.; a

, Osterman B. Isolation of Actinobaculum schaalii and schaalii of Actinobaculum Isolation Osterman , B. , .; .; w Sutter S, Frei R, S, Sutter R, Frei

F w : Springer; 2006. p. 430 p. : 2006. Springer; aredesLópez L, P P - o . Actinobaculum schaalii: Actinobaculum schaalii: r . o 388. [PubMed: 6501882] 388. [PubMed: P Hansen TM, Søby KM, Lund L, Prag J. Actinobaculum schaalii in urological patients, schaalii in patients, urological KM, Lund L, Prag Actinobaculum J. Søby TM, Hansen Y k - k V e pathogen or innocent bystander? A retrospect bystander? A or innocent pathogen e – v al i F y DH, Ruhn y DH, arez as assoli c guelin C, Genne D, Genne guelin C, v v aldmann KH. Pyelo KH. aldmann ork, N e anden Bempt I, Bempt anden ajkrt D, Simoons av n 20854424] schaalii, Austria. Eme by Actinobaculum 20587200] 67:282 2010; Infect North Diagn Dis. America. Microbiol in infection schaaliitract urinary [PubMed: 20542207] chronic renal patient with schaalii Pyelonephritis caused by Actinobaculum 22:438 2003; Clin Infect J Dis. obstruction. Microbiol Eur infection. Enferm 2012; 30:505 InfeccMicrobiol Clin. infection. Enferm tract children?Acta in infections Denmark. Eme patients, elderly uropathogen in 20031046] urinary tract infection in the elderly population. Bacteriological and clinical characteristics. 42:43 2010; Scand Dis. J Infect 22606634] Urol. [PubMed: 2012:468516. 2012; obser schaalii: clinical 15032264] 22209960] 267. [PubMed: i 22029906] 2011; [PubMed: 11:289. schaalii causing M. Actinobaculum [PubMed: 21508151] real screened with [PubMed: 21767246] Actinomyces, Actinobaculum, Actinobaculum, Actinomyces, M.; Y 3321562] Can suis. causedCorynebacterium by Morphological 1990; 18:595 r the Omsk in breeding herds suis in of boars Dtsch technique. immunofluorescence 93:381 P T V W Microbiol Spectr 271. Hoenigl M, 271. Leitner E, Hoenigl M, Bernar272. Larios OE, 273. Fendukly 274. 266. Andersen LB, Bank S, Hertz B, Søby KM, Prag J. Actinobaculum schaalii, a cause of urinary schaalii, cause of a Actinobaculum Prag B,J. KM, S, Søby 266.LB, Bank Hertz Andersen common schaalii, a Actinobaculum J. KM, Prag Søby A, TM, Hansen 267. S, Bank Jensen 268. Nielsen HL, Søby KM, Christensen J 269. 270. B 261. Cattoir 261. Cattoir 262. Tschudin 263. 264. S, Bank 265. Al 257. 258. Per M, Liebhold 259.FJ, Kaup 260. Plescha 255. Jones JE, Dagnall GJ. The carriage of Corynebacterium suis in male pigs. J Hyg (Lond). 1984; Hyg pigs. male J in suis Corynebacterium The carriage of GJ. 255. Dagnall JE, Jones 256. K Schaal, wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

e

– v

– i

omen omen age 41

as P w v ertebral ertebral n

49. 49. V

– aginitis: a aginitis: v

. 2011;

r aginalis.

athol. 1991; v P aginalis in the aginalisthe in 5308. [PubMed: 5308. astidious astidious ance, bacterial bacterial ance, v – f ev aginalis and aginalis ardnerella ardnerella 10775734] v g Muniesa ML. Urinary tract tract UrinaryML. Muniesa - . Lancet. 1968; 1:1112 Lancet. 1968; . ok C, Kliethermes S, S, ok Kliethermes C, v Esp Quimiote v Esp y F e eremia in a premature premature neonate. a eremia in c . 2009; 171:1012. [PubMed: 2009; . 171:1012. r 654. [PubMed: 16455938] [PubMed: 654. urinary microbiome: a microbiome: urinary w of thirty cases. cases. Obstet thirty w of – e diagnose and potentially i diagnose and potentially ge . Urinary tract infections in .infections in Urinary tract - gnan e

P icance. Pediatr Infect Dis. 1986; icance.Infect Pediatr vi 670. [PubMed: [PubMed: 17618471] 670. e 67. [PubMed: 24592798] [PubMed: 67. f e to aginalis in the urinary tract. tract. J Clin aginalisthe urinary in – – - omen. J Infect Dis. 1981; 144:114 1981; Infect Dis. omen. J v 1540. [PubMed: 22668653] 1540. [PubMed: White K, White . Urosepsis with Actinobaculum Urosepsis . w ay M, Flückiger U, Bassetti S. Bassetti M, Flückiger U, ay - – 712. [PubMed: 712. [PubMed: T g – e icult aginalis bact aginalis f illiams J. illiams Gardnerella

f v

W Castro MA, Jaime MA, Castro gnant - e

chülin aginalis as a urinary pathogen. J Infect. 1989; a J as urinary pathogen. aginalis v y urinary incontinence. MBio. 2014; e01283 5 2014; MBio. urinaryincontinence. y y R, c ere phimosis as cause of urosepsis with cause of as urosepsis ere phimosis aginalis in human J Clin urine. inAm aginalis human k all DM. Bacteriuria due to ureaplasmas and other and to other due ureaplasmas all DM. Bacteriuria v v alence signi and alence ani A, Gaughan J ani Gaughan A, olfe AJ. The female e w all DR. Bacteriuria due to Ureaplasma urealyticum urealyticum Ureaplasma to due Bacteriuria all DR. gen

w o ev . J Clin Microbiol. 2005; 43:5305 Microbiol. 2005; Clin J . r W w y , Gilbert GL. Anaerobic and other and other Anaerobic GL. , Gilbert o . 2012; . 174:1539 F r bacteria in urinary tract disease: urinary tract in bacteria

uladhar H, Karki BM. Urinary tract infection in in infection tract Urinary H, BM. Karki uladhar y: pr aginalis bacteremia: a r bacteremia: a aginalis alence of Gardnerella of Gardnerella alence ge , Chat , c T , McD y K v e P ailable in PMC 2016 June 01. e F ev v icance in a hospital population. Obstet Gynecol. 1988; 71:245 1988; Gynecol. Obstet population. icance ina hospital , McD

. Septic shock caused by Gardnerella Gardnerella caused by Septic . shock a f F P

gnan airl y K . Pr omen with preeclampsia. J Infect Dis. 1983; 148:605. [PubMed: 1983; Dis. 148:605. J Infect omen with preeclampsia. e Andresen K, Klemmensen B, Højlyng N, Sørensen SH, Sørensen Højlyng B,N, Klemmensen Andresen K, F e F entional ell Gardnerella R. er L, Gai X, er L, Gai X, w y K v k k e aard Fernández MB, García n 1133. [PubMed: [PubMed: 3260242] 1133. al of Gardnerella al Gardnerella of airl 865. [PubMed: 6604191] [PubMed: 865. -

587. [PubMed: 12368979] [PubMed: 587. g y K ginalis in infections of the urinary tract. J Infect. 1989; 18:45 1989; tract. of J Infect. in the urinary infections ginalis – , Demmler GJ. Gardnerella GJ. Gardnerella Demmler , F –

– iv e , Nyirjesy , Nyirjesy a ed. Nepal Med Coll J. 2013; J. 15:65 ed.Med 2013; Coll Nepal Actinobaculum schaalii: a di schaalii: Actinobaculum airl 172. [PubMed: 172.6610845] [PubMed: F and signi eltman S, S E, Meuleman eltman v k Y

– F V emp M, airl . Unco F

K , Schaeren S, Laifer G, Frei R, Batt G, R, Laifer Frei S, Schaeren , F asymptomatic bacteriuria in pr in bacteriuria asymptomatic . Surv , yn SJ. Suprapubic aspiration of urine pr urine in of yn Suprapubic aspiration SJ. erloo T F F aginalis in aginalis k en cases of Actinobaculum schaalii infection: clinical rel clinical infection: Actinobaculumen schaalii of cases omen omen with and without u v ov S243. [PubMed: 3491981] S243. [PubMed: T aginosis. Obstet Gynecol. 2000; 95:710 Gynecol. 2000; aginosis. Obstet Dossary Author manuscript; w

– - v . anisms during pr anisms ger PC, Bruba ger r g an Eijk J, Garland SM, Garland SM, o M, González r

V , Collins LE, Collins , Mas , Birch , D . Gardnerella .

av anisms anisms in F W 239. [PubMed: 239.1992615] [PubMed: 193.2809241] [PubMed: enbe g W A, Gilbert GL, A, Gilbert all DR, Buchanan JD, DR, all Buchanan JD, , Bruderer , Bruderer r – – Br 53.21412672] [PubMed: k J R ication, and antibiotic and susceptibilit ication, P A - y 23:862 1983; Int. w f – y K e e o ía

e adyen IR, Ey adyen k F vige vige a astidious o airl Schrec comparison of e14. 64:170 Gynecol. 1984; La Ugeskr Cesarean section. species Peptostreptococcus after 19284925] 22:585 2002; J Perinatol. f 5(Suppl):S239 and Gardnerella 6604763] microo 7276624] 122. [PubMed: 4171842] 1114. [PubMed: Kidn with bacterial 95:234 urinaryincidence tract: 3257296] 250. [PubMed: 19:191 [PubMed: 2783715] Microbiol.26:1130 1988; Christensen JJ. Christensen JJ. identi 16208004] R elderly patient. schaalii in an by Actinobaculum infectioncaused 24:52 J Clin 44:652 2006; schaalii Microbiol. and Aerococcus urinae. caused osteomyelitis by Dis. 26:667 Infect 2007; Microbiol J Clin Eur uropathogen. condition often Actinobaculum schaalii. Ugeskr La Actinobaculum schaalii. Ugeskr F Microbiol Spectr 292. Pearce MM, Hilt EE, Rosenfeld AB, Zilliox MJ, Thomas MJ, Zilliox EE, AB, Rosenfeld 292. MM, Hilt Pearce LB. Gardnerella Reller 293. LG, Reimer Kjaeld 294. K, Charib Datcu R, Al 295. Amaya RA, 287. Gilbert GL, 287. Gilbert 288. S 289. McD 290. Mc 291. 281. Harmanli OH, Cheng G Cheng 281. OH, Harmanli Birch 282. MH, D Lam J, Sturino Thomason K, Zabrans S, 283. Josephson 284. Clar 285. Sturm Birch 286. MH, D Lam 277. Garc 278.PD, Sturm 279. Haller Bhattarai S, Mandal PK, R, 280. Amatya 275. Jöhnk ML, Olsen AB, Prag JB, JB, KM. S Søby Olsen AB, 275. Prag ML, Jöhnk J, M, 276. Prag Reinhard wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

.

age 42 ransm P T

wth in wth in x o

year year e -

e v i aginalis ymicrobial v 79. [PubMed: 79. aginalis aginalis y of – v v p xpósito Aguilera M. xpósito Aguilera aneechoutte M, aneechoutte M, w of episodes. 49 , Hossain Hossain H, , . Gardnerella Gardnerella . e V T 368. [PubMed: Y vi

– e A, E A, J 91. [PubMed: 8460355] 91. [PubMed: yticus? Clin Infect yticus?Dis Infect Clin . J Clin Microbiol. 1989; Microbiol. Clin . J – r h y an male. of and adult brain 569. [PubMed: 6386869] 569. [PubMed:

e ger H, Pitlik gerPitlik S. H, F use rop Geogr Med. 38:137 1986; Geogr rop – aginalis from blood the by aginalis from r aginalis bacteremia after after aginalis bacteremia b T v v es females and males and is and is males es and females erstraelen H,

atzel C, Hain atzel Hain C, icance of polymicrobial gr icance of polymicrobial 435. [PubMed: [PubMed: 24016769] 435. v f V – 263. [PubMed: 263. 21051845] onisbe ol W

associated balanoposthitis. S balanoposthitis. associated – aginalis septicaemia septicaemia with aginalis v K aginalis after endometrial ablation. endometrial after aginalis - v n v Bernard K. Gardnerella Gardnerella Bernard K. ransm Dis. 18:76 ransm 1991; videncia stuartii: r videncia stuartii: T

o Biol. 2003; 108:229. [PubMed: 12781418] [PubMed: 108:229. Biol. 2003; ylococcus possessing antigen 51 as agents of antigen ylococcusas possessing 51 agents

ylococcus saprop ilm i ilm x h f e h aginalis , Labbe M, Glupczynski Glupczynski Labbe , M, v omen: the LUTIW project. Scand J Prim Health Health J Prim project. omen: the LUTIW Scand iebe iebe D, P 253. [PubMed: 13922034] [PubMed: 253. w Stap ery Gardnerella of W – emmerman M. The epidemiologyof emmerman bacterial 2010; 70:256 2010; , Swidsinski , S, Swidsinski --

,

Gardnerella Gardnerella T ication of pathogenic bacteria and pol bacteria and of pathogenic ication ov V T f , Blanc B. Garnerella Garnerella Blanc ,B. , Schanen A, Michel S. Gardnerella Gardnerella Schanen,Michel S. A, er M, Z, Samra er e F

P est. k DJ. Gardnerella Gardnerella DJ. onforti N. The The signi N. onforti . BMC Infect Dis. 2010; 10:81. [PubMed: 20353563] [PubMed: Dis. 10:81. 2010; Infect . BMC k v r 1338. [PubMed: 22752597] 1338. [PubMed: K n – . Rec vira Lledos J, Martinez Martinez Martinez viraLledos J, urschner S, Kühle S, urschner J,

P o T 567. [PubMed: 9323466] 567. [PubMed:

vmecillinam compared with placebo thera placebo compared with vmecillinam wulf G, Mazars E, Cattoen C. Gardnerella Gardnerella C. G, Mazars E, Cattoen wulf e strains of stap e strains i ailable in PMC 2016 June 01. – viou Bauc . Gardnerella . Gardnerella e v . Gardnerella bio - v a , R , i y man: case report and characterization of the isolate. J Clin J Clin ythe isolate. characterization of and case report man: a P W oulouse, France. S oulouse, France. W at 657. [PubMed: 21097741] [PubMed: 657. h , D , Bretelle , Bretelle artz D, A T g – aginalis carriage in male patients. patients. male aginalisin carriage F F e v w w 224. [PubMed: [PubMed: 8578355] 224. n aneechoutte M, aneechoutte M, - o – V prostatic adenoma. J Infect Dis. 1990; Dis. J 161:367 adenoma. Infect 1990; prostatic athol. 1962; athol.15:252 1962; , Bauriaud R, Bertrand MA, Blanc C. Clinical and microbiologic microbiologic and C. Clinical Bauriaud Bertrand , R, MA, Blanc 806. [PubMed: 806. 18057138] xual beh

orn C. Bacteremia due to due Pr to orn C. Bacteremia P , Loening , P – , Sch e independent identi independent k - Y T e endocarditis and septic emboli in the kidn in the and emboli septic e endocarditis v . Eur J Obstet Gynecol Reprod Reprod J Obstet Eur . Gynecol unin CM. Who are you are unin CM. Who i y 89:221 . Gynecol Obstet I Obstet Gynecol . fel fel K 57. [PubMed: 17354160] 57. [PubMed: 162. [PubMed: 3490001] 162. [PubMed: f viously healt viously y ulka – – e aeters A, Leenaerts L, Gilbert Leenaerts aeters A, gneur J wer urinary tract infection in infection tractwer urinary r K o , López Onrubia López , erhelst R, erhelst R, w vici L, Huminer D, Druc vici L, Huminer D, Author manuscript; , wie WR, Ch WR, wie , Dryja DM, Dillon W Dillon , DM, Dryja e

T 898. [PubMed: 15736028] [PubMed: 898. o . Culture . V . r xuall o atanakuna Y – T e aginalis bacteremia in an adult male. Eur J Clin Microbiol Infect Dis. 1997; 16:400 1997; Dis. Infect Eur J Clin Microbiol male. an adult in bacteremia aginalis study of bacteraemic urinary tract infection in a single institution. Eur J Clin J Eur single institution. a in infection urinarytract of bacteraemic study W v e direct plating method. J Clin Microbiol. 1984; 20:568 J Clin Microbiol. method. e plating direct e iens PR, Ng B, Reimer A, Burdz Burdz A, Reimer PR, Ng B, iens

5510. [PubMed: 14662931] 5510. [PubMed: 1134. [PubMed: 2787333] 1134. [PubMed: v ilá M v Igra Igra i , Schilling , J, Schilling Mendling i – – - V W V - ferent doses and duration of p andof duration doses ferent yel GA, Drouet EB, De H Montclos De EB, yelDrouet GA, f vre JC, Lepa JC, vre o wdhury MN. Gardnerella MN. Gardnerella wdhury acé e gman o g grand JC, Al JC, grand oods TD, oods TD, e 7:1132 aginalis bacteremia from pulmonary abscess in a male alcohol a alcohol male a inpulmonary from abscess aginalis bacteremia s to in aginosisrelation aginal myomectom yelonephritis, infect e erstraelen H, erstraelen oon HJ, Chun J, Kim JH, Kang Na SS, J, JH, oon Kim HJ, Chun orres Coagulase Pereira A. orres prospect Dis. Microbiol 16:563 Infect 1997; South Med1996; J. of di l uncomplicated Care.25:49 2007; Chakraborty Clin 2003; Microbiol. J recipients. transplant tractrenal genitourinary of infectionsthe in 41:5500 140. [PubMed: 3488607] 140. [PubMed: Dis. 1986; 13:159 in men features in of urethritis 1907404] 2005; 40:896 urinary infection. J Clin Dis. 25:85 1993; J Infect Scand true infection. urine: contamination or 401. [PubMed: 9228486] 401. [PubMed: a man with inbacteremia 1688908] v 2 Lemm s transmitted v Arch Gynecol Obstet. 2012; 286:1337 2012; Obstet. Arch Gynecol v 43:434 2013; Mal Med a male inbacteremia Infect. patient. p Int 2010; 21:653 J STD AIDS. a pr inbacteremia Microbiol.46:804 2008; Garderella quantitat W T V Y Microbiol Spectr 314. outcome bacteriological Clinical and SE, TJ. H, Lundholm R,Holm Stenlund 315.Monsen Ferry SA, Hong G, C, 316. E, Imirzalioglu Domann 308. Burdge DR, B 308. DR, Burdge 309. Lef R, 310. Colodner Raz R, 311. 312. Si 313. Leib Bishara J, 303. Den 304. L A, Doer 305. Swidsinski 306. 307. Ch 298. Agostini A, Beerli M, Franchi M, Beerli Franchi A, 298. Agostini EK, Bonnet I, Canis 299. Alidjinou 300. 301. La 302. Bastida 296. La Scolea LJ J 296. La Scolea DM. Bacteremia of DeDonato 297.RA, McCool wis e and L Kline

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

. J . r , P an G, age 43 v Kreft

309. P - A 876. 876.

– ger ger – r bladde

einstock einstock isco ab W V enbe w . Decreased er L, Gai X, er L, Gai X, ork. The , k k ersity of the the ersityof W w W v alence of alence of i einstock GM, ev gren E, omen. Zentralbl Zentralbl omen. e e MJ. The human ered: metagenomic ered: metagenomic r W k w xually xually transmitted ransm Dis. 2015; Dis. ransm e ov T rautner B ER, Bruba

x T 308. discussion 308 308. discussion e , gnant – erhelst R, Schuren FH, R,FH, erhelst Schuren

A amplicons. BMC A amplicons.BMC F y s on e V c N en A, Melton MS, Lucia older people. J Am Geriatr Soc. Geriatr Am people. J older , F ers. S ov anisms in anisms Men Urologic with aran S, Sode

k an der Pol B. The an The microbial B. der Pol g gnan

w 71. [PubMed: 18336452] [PubMed: 71. r V e or – Mi D, Rong R, Mi D,R, Rong

ic urethritis in men. J Microbiol in ic urethritis men. . Impact of infection on the secretory on infection the secretory .of Impact , f w

P , Ramig R W x obsen KS. Assessing d obsen Assessing KS. . J Clin Microbiol. 2014; 52:871 Microbiol. 2014; J Clin . F , Smith AL, Rogers R, Nolen TL, Nolen R, , Rogers AL, Smith r e k an Bokh an ated bacteria in the adult female female the adult in ated bacteria v W iv an B, Eas an B, 596358] C, C, ers GJ, Huisjes HJ. The pr Huisjes ers HJ. The GJ, F eidner v , 2016 June 01. e White KJ, Richter HE, Nager Richter White C Nager HE, KJ, er L. Pelvic Floor Disorders Net L. Pelvic er Floor W

- V S k

, - r T ortenberry JD, , Sung V , Sung an B, Katz an Katz B B,

F P ] F adze E, Ndayisaba G adze E, Ndayisaba

Independent Analysis in the MAPP Research in Analysisthe MAPP Independent - logia. 2008; logia.40:66 2008; , Jacobson SK, Marchesi JR, Dra iv X, X, anna anna K P oided urine of asymptomatic adults. Front Cell Infect

v enton K, Fitzgerald M, Mueller ER, Schrec ER, M, Mueller K, Fitzgerald enton vts ev ork. Search forork. Microo Search i , Domann E. Hidden unc pathogens E. Hidden Domann , 36. [PubMed: 24296328] 36. [PubMed: K E, oh y urinary incontinence. Am J Obstet 2015; yGynecol. Am incontinence. urinary w T – , Diemer , Diemer c T 267. F ailable in PMC

– , Ts A in v 447. [PubMed: 2128698] 447. [PubMed: 135. [PubMed: 25 135. [PubMed: a olfe AJ, olfeBruba AJ, gen N – W 1383. [PubMed: 22278835] [PubMed: 1383. – r 161. [PubMed: 17446965] [PubMed: 161. fer J, Moalli J, fer Moalli C, Ajami NJ, Petrosino J – W f – A er L. Evidence of uncult of er L. Evidence it F features of persistent nonspeci features of k . Bacteremic urinary tract infection in urinary infection tract . Bacteremic W aginal microbiota in african s in microbiota african aginal W v ate A. Microbiological study of urethritis in men attending STD clinic. a attending men in urethritis A. study of Microbiological ate ger PC. Urine is not sterile: use of enhanced urine culture techniques to to techniques culture use enhanced urine of Urine sterile: is not ger PC. o illiams illiams J, White agenlehner agenlehner g r , Aarnoudse JG, Meije an der Pol B, der an irst catch urine are highly similar to those in paired urethral s paired in urethral similar those to urineare highlyirst catch oh E, Diao L, Gao L, Gao E, Diao oh , Chakraborty , F , Gai X, , X, Gai f W 367. [PubMed: 26048203]

W V T , Mapes T F – T g AL, Brauner A. Estrogenic action on innate defense mechanisms in the defense mechanisms innate action on Estrogenic g AL, Brauner A. enbe r k y K, Pearce MM, Rosenfeld AB, Zilliox MJ, Mueller MJ, yAB, Zilliox Rosenfeld Pearce MM, K, ainA Culture Syndrome: xually transmitted infection. PLoS One. 2010; 5:e14116. [PubMed: 21124791] [PubMed: One.5:e14116. infection. 2010; PLoS xuallytransmitted e e P Author manuscript; ortenberry JD. Bacterial communities of the coronal sulcus and distal urethra of of urethra and sulcus distal the coronal of communities ortenberryBacterial JD. ortenberry JD. Characteristic male urine microbiomes associate with with associate urine ortenberryCharacteristic male microbiomes JD. wn R, ersity associated with urinary tract infection in a trial of bacterial interference. J

933. [PubMed: 8708302] [PubMed: 933. erwijs MC, erwijs MC, . F o F v – an Der Pol B, Dong Q, an R B, Der Pol V i 347.e11. [PubMed: 26210757] [PubMed: 347.e11. V Meikle S oh E, Shibata N, Rong R, oh E, Shibata N, 2011; 11:244. [PubMed: 22047020] [PubMed: 11:244. 2011; – Mensink W T f H, f 152. [PubMed: 152.25668647] [PubMed: A, Br f , Hirschbe – P D gren E, ork. J Urol. 2015; ork. 194:127 J Urol. ijgert JH. The impact of hormonal contraception and pr contraception hormonal The impact of ijgert JH. v YB. Microbiological Microbiological v YB. r ert J, ert J, aard IE, Barber MD, Scha aard IE, Barber el JC, Stephens A, Landis JR, Chen J, Mullins JR,Stephens Landis J, el A, Chen JC, o w k ermann RJ, Monroe P RJ, Monroe ermann gdor g k W k r allace D, olfe AJ, Schrec wis olfe AJ, olfe AJ, an e v Chronic Pelvic Chronic Pelvic Net J Urol.35:299 2009; glands. Braz male Int accessory the capacityof [PubMed: 19538765] Infect.2007; 40:157 Immunol Andro infections. tract analysisurinary of Indian 1990; Res. J Med 91:443 de cervic infectionson and 42:143 77:32 2014; urinary tract. Maturitas. 1996; 44:927 Ny W u microbiome in female urinary 213:347.e1 Research MAPP Net R,GD. Ehrlich GM, GM, Diao L, asymptomatic s communities in male 21603636] [PubMed: One.specimens.6:e19709. 2011; PLoS Sode [PubMed: 22606251] 7:e36298. 2012; One. PLoS adolescent males. W bladde female inthe adult flora detectbacterial resident [PubMed: 24371246] female urine microbiota by high throughput 16S rD sequencing bythroughput of microbiota high female urine Microbiol. urinary microbiome; bacterial D [PubMed: 23967406 Microbiol.3:41. 2013; microbiota d Infect. 71:358 2015; pr from obtained bladder in aspirates bacteria anaerobic suprapubic 1979; A]. 244:260 Bakteriol [Orig Dong Q, Nelson DE, Bruba Clin 2012; 50:1376 Microbiol. W Microbiol Spectr 331. Marconi M, Pilatz A, Pilatz A, 331. Marconi M, 332. I C, Hain 333. Imirzalioglu Go L, Deodhar 334.A, Pillai 327. Lüthje 327. Lüthje 328. Ac AB, Thomas 329. MM, Rosenfeld MJ, Zilliox Pearce 330. Nic 323. Dong Q, Nelson DE, DE, 323. Nelson Dong Q, 324.DE, Dong Q, Nelson EE, 325.McKinl Hilt 326. Bo 318. Siddiqui H, Nederbragt AJ, Lagesen K, Jeansson SL, Ja Lagesen K, Jeansson Nederbragt 318.AJ, H, Siddiqui 319. L 320. Horwitz D, McCue 321. Dan 322.DE, Nelson 317. wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

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e P 82. 82. apore, 300. athol – vin L. vin g 721. – P e –

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Iglesias M. F omen.

associated associated - - w 2002; 6:78 2002; 1379. [PubMed: 1379. e303. [PubMed: – – . 2011; 17:720 2011; . , Rossini A, , Rossini r abre R, Philippon R, A. Philippon abre ery old ery old , Carlet J. J. Carlet ,

V F v

P , Salmon D, ,Guill Salmon erbau Hospital, Sin erbau Hospital, , Rodriguez

V

P K atti a N. caused by Urosepsis P w . J Infect Dis. 1979; 140:653 1979; Infect Dis. J . a y

c

Martos

yelonephritis with associated associated yelonephritis with - y transplant recipient: case report. case yreport. recipient: transplant p e O860. [PubMed: 24773457] O860. [PubMed: gnan ares M. Cystitis and haematuria due due haematuria and M. ares Cystitis Arthritis Rheum. 2011; Rheum. 41:297 2011; Arthritis 454. [PubMed: 454.213495] [PubMed: – e obsen KS. Alterations of microbiota in of in microbiota obsen Alterations KS. – iv k

007364. wn WJ, Allen SD. Diagnosis and Diagnosis etiology SD. Allen wn WJ, 7892090] ert J. The presence of antibody ert J. The of presence - w species causing chronic urinary tract tract chronic causing urinary w species

. Actas Urol Esp. 2009; Esp. 33:909 Urol 2009; Actas . o k , Garcia e P w 20534304] e a v 2012 gelii in an adult: case report and literature and literature r case report adult: an in gelii vi e Care Med. 2003; 29:1376 Care 2003; Med. e - o e ajardo Ol , Dan e r v i F F 330. [PubMed: [PubMed: 10968108] 330. 3941. [PubMed: [PubMed: 12409355] 3941. – – 277. [PubMed: 277. 18987176] 831. [PubMed: 831.24275738] [PubMed: atel R. Actinobaculum bacteremia: a report of 12 cases. of a 12 bacteremia: atel report Actinobaculum R. – – gel MD, MD, Br gel P Casan r - aillot J, Aouizerate J, Le Guern Guern J, Le Aouizerate aillot J, . Lactobacillus delbrueckii as the cause of urinary tract the cause tract of as urinary delbrueckii Lactobacillus . 1152. [PubMed: ystitis. BMC Microbiol. 2012; 12:205. [PubMed: 22974186] [PubMed: 12:205. Microbiol. 2012; ystitis. BMC pr during bacteriuria w of literature. J Infect. 2005; 51:e299 Infect. 2005; literature. J w of P V ailable in PMC 2016 June 01. c – 554. [PubMed: 22080192] 554. [PubMed: e a Prado L, gson D. Bloodstream infections due due to spp.: gson D. BloodstreamPeptoniphilus infections v 4313. [PubMed: 21976754] 4313. [PubMed: – a e g caesarean septicaemia in Kandang Kandang in caesarean septicaemia 1368. [PubMed: 1368. [PubMed: vi , Marin – Misset B, Ali AB, Gattolliat O, Meria Meria Ali O, AB, Misset Gattolliat B, - yelonephritis and secondary bacteraemia caused by caused bacteraemia and yelonephritis secondary e e – w of the literature. Semin Semin literature. w of the P p V e , Gr , , vi , Lochet A, Prots L, Félice R, Senescau A, Senescau A, R, , Prots L, Félice A, Lochet T T Lobato O, Hernángomez S, Hermida A, Guinea J, Marín M, Peláez Marín Peláez M, Guinea J, A, S, Hermida Lobato O, Hernángomez 142. [PubMed: 20605373] [PubMed: 142. e P - – Marin Marin as interstitial interstitial

, Ohkusu K, Kitazono Hosok ,Sogi M, H, Ohkusu - geas M, geas wn origin. Pediatrics. 2001; 107:E11. [PubMed: [PubMed: 11134475] 107:E11. 2001; Pediatrics. wn origin. r . Acute r T ynch ynch ev o yle B, Arnold D. Pyelonephritis caused by Corynebacterium minutissimum. by Corynebacterium caused yleArnold D. B, Pyelonephritis

Y O L o - . 2012; 18:552 2012; . r . BMJ Case Rep. 2012 pii:bc Rep. 2012 Case BMJ . , D , Azna , y ransm Dis. 2013; 40:829 ransm abdominal infections due to Gemella species. Int J Infect Dis. J Infect Dis. Int species. due to abdominalinfections Gemella F - Author manuscript; c W T

. tafson DR, Rosenblatt JE, omen omen with x ystitis due to Corynebacterium urealyticum in a patient with ANCA patient with a in urealyticum ystitis due to Corynebacterium er of er unkn of e c , Arakaki w , Petroelje BK, Doern G , Petroelje BK,

v ers GJ, Aarnoudse W Mensink ers JG, GJ, Aarnoudse gnan Y e v 15 cases. Clin Microbiol 20:O857 Infect. 2014; Microbiol cases. Clin 15 e A, Bottone E, Herold BC. Peptostreptococcus asaccharolyticus renal abscess: a rare a abscess: rare asaccharolyticus renal Peptostreptococcus BC. E, Herold Bottone A, , Garrouste , W

e Chemothe V V aris). 2012; 60:140 aris). 2012; Lechuz Cu JM, Lechuz S , Jacob SC, Lim SH. Post SH. SC, Lim , Jacob Sanchez 1995. Med J Malaysia. 1997; 1997; 52:325 J Malaysia. 1995. Med - - P P - r – K K, Church D, wn nongonococcal urethritis. J Infect Dis. 1978; Dis. 138:445 J Infect 1978; nongonococcal urethritis. artz SL, Kraus SJ, Herrmann Kraus SJ, Herrmann artz KL, Sta SL, o ransplant Proc. 2010; 42:1367 ransplant Proc. asculitis: case report and case report r asculitis: agihashi agihashi w ontana I, Bertocchi M, Rossi AM, Gasloli G, Santori G, Ferro C, C, G, Ferro Santori G, AM, Gasloli BertocchiRossi ontana I, M, agnoux R, Bérezné A, C, Damade eo Urethritis due to Corynebacterium glucuronolyticum. Chemothe glucuronolyticum. J Infect Urethritisto Corynebacterium due [PubMed: 21437677] urethritis. S of Microbiol. 40:3938 infection. 2002; J Clin J Clin 49:4311 2011; Microbiol. [PubMed: [PubMed: 19900386] J. 13:1151 Pediatr Infect1994; Dis pediatric a kidn urealyticum in infection Corynebacterium T Encrusting v [PubMed: 21277617] ri Corynebacterium and sanguinis J Infect anaerobic bacteria in asymptomatic in asymptomatic bacteriaanaerobic 118996] 658. [PubMed: BouzaE. Extra [PubMed: 12044308] and r report a case bacteraemia: 16321644] D2. Corynebacterium Intensshock caused by 12830376] striatum. r case report and Corynebacterium A cause f of 1993 report of in infections tract agent of probable urinary delbrueckii: Lactobacillus Biol ( 47:275 Microbiol. infection. 2009; J Clin during pr urine from Abdolrasouli A, Roushan A. Corynebacterium propinquum associated with acute, nongonococcal associatedpropinquum acute, nongonococcal with Corynebacterium Roushan A. A, Abdolrasouli F P T Y Microbiol Spectr 351. Galan 352. 353. S a D. massiliae,” n 354.G, “Actinobaculum Greub Raoult Gus E, 355. Gomez 347. Craig J, Grigor 347. Grigor Craig J, 348. 349. M, Otsuka 350. Matusnami 343. García minutissimum 344. KM. Corynebacterium NM, Ahmad Ahmad 345. Audard M Ruiz Gil López 346.A, Beteta 337. 338. Br Soh 339.M, Njomnang Bernier 340.B Darbro 341. 342. Meije 335. Siddiqui H, Lagesen K, Nederbragt AJ, Jeansson SL, Ja AJ, Jeansson Nederbragt Lagesen 335.K, H, Siddiqui 336. Casullo wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

- e

age 45 v ,

P i F

Clin Clin ransm y CK. omen omen

e T x PCR x w

e . 1995; x y e airl

ransm Infect. ransm xually xually F icance, and icance, utr Boles. T f e . S aginalis 544. [PubMed: 544. V y , Ouaki , C Ouaki x v – e T ys. ealing a renal a ealing renal atholog a multipl e v P e

, Marrazzo JM, Fredricks JM, Marrazzo ,

omen. Int J STD AIDS. omen. Int

T w nosed by routine routine urine nosed by

, Landois Landois ,

P d cervicitis among among cervicitis d ang H, Gilbert ang Gilbert GL. H, W . 1997; . 122:542 annuti CM, Romito Romito GA. annuti CM, r 1877. [PubMed: 19357202] [PubMed: 1877.

949. [PubMed: 24220356] [PubMed: 949. P h – –

oided urine and urethral and and urethral urine and oided alence, clinical alence, signi clinical v yelonephritis r - ev p 449. [PubMed: 9773441] 449. [PubMed: – wn cause of septic J Intens wn cause shock. of septic , Bouillard Bouillard , irst o f V sociation of Leptotrichia/Sneathia spp. Leptotrichia/Sneathia of spp. sociation ochensc arth L, Garland S, Denham I, S, Garland Denham L, arth

infected and men W v - xual men: a case xual a case control stud men: , Depner K, Fiedler Depner , ere infection bernardiae: due to Actinomyces ere infection anisms in anisms urine of by use e

, Freedman E, , Freedman v g by Mycoplasma hominis. by Mycoplasma errier W . Mycoplasma genitalium urethritis in men. Int J men. in genitalium urethritis . Mycoplasma

F r e , Rabelo MS, , Rabelo MS, aginalis is associated with other s other is with associated aginalis

462. [PubMed: 16326846] [PubMed: 462. iebe D, Bernard K. Gardnerella Gardnerella K. Bernard iebe D, ysematous V T aginalis in the urethra of Indian men. Indian J men. Indian Indian urethra of aginalisthe in P 326. [PubMed: 6364406] 326. [PubMed: v – h , v – W F S27. [PubMed: S27. [PubMed: 15364301] , ong la la esical actinomycosis diag actinomycosis esical – T 158. [PubMed: 8824986] [PubMed: 158. 203. [PubMed: 7251284] [PubMed: 203. K v yeri, unkn an – – e guchi guchi

actinomycosis associated with bilateral necrosing renal necrosing bilateral with associated actinomycosis e

ransm Dis. 2013; 40:944 ransm 1):S23 659. [PubMed: 20715676] 659. [PubMed: v of N. the kidnMycoplasma infections T – ailable in PMC 2016 June 01. w C, Lee D, Hor w C,Lee D, o v a x y man: case report and characterization of the isolate. J ythe isolate. of characterization and case report man: a yte esterase testing of yte testing of esterase . Renal . Renal e , H. Goossens S ransm Dis. 25:448 1998; ransm r unilateral emp unilateral c h P

T ezhd er I. Gardnerella er Gardnerella I. oz H AM, Artese ener Z, Kadioglu A, Ang O. Bacterial pathogens in male patients inpatients male Ang O. pathogens A, enerBacterial Kadioglu Z, x k F v . J Clin Microbiol. 2009; 47:1871 2009; Microbiol. . J Clin yelonephritis caused e ov y p ec vrat Q, Guillaume Guillaume Q, vrat aik SS. Primary aik SS. Primary 806. [PubMed: 18057138] 806. yelonephritis. Dtsch Med yelonephritis. Dtsch Med e 254. [PubMed: 254.8088884] [PubMed: as in bacteria men: associated P – p W - – ul. S ul. anisms in the male urethra. Zentralbl Bakteriol Mikrobiol Hyg [A]. 1988; [A]. Hyg Zentralbl Mikrobiol Bakteriol in the anisms urethra. male b 165. [PubMed: 15800097] g r ication of 14 genital microo of ication 14 – f ransm Infect. 2005; 81:458 Infect. ransm a Bel C, . Acute viously healt viously gonococcal urethritis in heteros in gonococcal urethritis v T e abrizi S, Bradsh abrizi - . PLoS One. 2014; 9:e98271. [PubMed: 24870125] . 9:e98271. One. 2014; PLoS Y idan Gü idan A, o en J, Gentens J, en Gentens Horn M, Menninger M, Held E, Heesemann J. Mycoplasma hominis. A rare J. E, Heesemann Mycoplasma Menninger Held Horn M, M, f T x - w v k aginosis e Author manuscript; , Jun YJ, , e e

838. [PubMed: 18073017] [PubMed: 838. 113. [PubMed: 3414078] [PubMed: 113. v aç . ransm Dis. 1983; 10(Suppl):323 ransm 78. [PubMed: [PubMed: 15681728] 78. – – g ala vi W aiphei K. Renal actinomycosis. BMJ Case 2014 pii:bcr2014205892. BMJ Rep. aipheiactinomycosis. Renal K. asuda M, Ito S, asuda Maeda S, M, D S, Ito T – e T uen K

C. Occurrence and pathogenicity of Mycoplasma hominis in the upper urinary tract: a tract: in hominis urinary the upper of pathogenicity Mycoplasma and C. Occurrence V Y erho C,L, Chambrone x Y iens PR, Ng B, Reimer A, Burdz Burdz A, Reimer PR, B, Ng iens ,

erse line assa line erseblot A e V Hartmann Hartmann AA, A P smears to identify Mycoplasma genitalium identify to Mycoplasma smears . Acta Cytol. 2010; 54:658 Acta Cytol. . v 63. e agent of acute e agent a I, a I,

, W y e – 63. [PubMed: 63.7603755] [PubMed: v v - . S . P i al – o , Read TH, , Read w echnie ML, Hillman R, Couldwell D, Hillman ML, R, echnie w e P a acé K en M, en M, g vi ong SS, ong SS, v umar B, Sharma M. Carriage of Gardnerel M. umar B,Carriage Sharma ytolog ydin MD, A ydin MD, e alk L, Fredlund H, Jensen JS. Signs and symptoms of urethritisan and Signs Jensen JS. alksymptoms L, Fredlund H, e transmittable transmittable microo 269:56 infection. S trachomatis or Mycoplasma Chlamydia genitalium with or without 2005; 81:73 cervical 2007; 18:835 Antimicrob 24(Suppl 2004; Agents. systematic r 1988; 27:110 causat 9190301] r 27:61 transmission. S papillitis. Int Urol Nephrol. 1980; 12:199 Nephrol. 1980; Urol papillitis. Int of course Lesieur O. Fulminant m caused by actinomycosisActinomyces 25878793] [PubMed: Care.2:42. 2014; c 22:157 1996; Infect Dis. case Clin report. a after periodontal bloodstream procedures: in the pathogens periodontal Dissemination of with urethritis in Istan in with urethritis of non Symptoms Infect. 81:163 2005; Med 1994; 99:252 Res. Simultaneous identi based r DN. Bacterial S with urethritis. nongonococcal bacteremia in a pr in bacteremia 46:804 Microbiol. 2008; F W Horliana Horliana A K Microbiol Spectr 374. E. Leuco Kihlström 375. M, Högdahl 376. Ishihara S, 368. Angel Abele 369. Küchle C, 370. Thomsen 371. pr Mycoplasma JS. genitalium: Jensen Loré B, 372. C, Anagrius 373. Elsner 362. Agr L J J, Surján 363.J, Galambos Juhász M, L 364. Leloup Herbland A, Na 365.SM, Jang 366. I 367. 357. 358. Iser 359. 360. Mc C Gillespie C, Liu 361. LE, CM, Khosropour Manhart 356. La wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript

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P ylori: ylori: 1101. p – elch RA. murine murine onaka H, onaka H, K W 18. [PubMed: [PubMed: , – Y 221. [PubMed: 221. 492. 492. – –

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. 2006; 70:192 2006; . . 2011; .17:487 2011; r v e ransm Infect. 2009; 85:15 2009; Infect. ransm T x e 67. [PubMed: 12823810] [PubMed: 67. – , Furubayashi K, Shimamura M, Maeda Shimamura Furubayashi , K, .; Mendz, GL.; Hazell, SL., editors. Helicobacter editors. Helicobacter Hazell, SL., .; Mendz, GL.; vitt M, Stamm WE. Clinical and microbiological features features microbiological Clinical and WE. M, Stamm vitt serine deaminase to modulate infection of the the of infection to serine deaminase modulate T alence of genital Mycoplasma, Ureaplasma, Gardnerella, Ureaplasma, Mycoplasma, alence of genital T - a L Ke ev ailable in PMC 2016 June 01. w wind O. Sortases and the art of anchoring proteins to the proteinsto the art anchoring the of and O. Sortases wind v a e , H a g A. Mycoplasma genitalium is associated with symptomatic and and symptomatic genitalium associated is with A. Mycoplasma y

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W e bacteria. Microbiol Mol e Biol R bacteria. Microbiol Mol virus infection. J Infect Chemothe J Infect virus infection. a v C, i A virus in Japanese men with urethritis, and risk urethritis, and risk with Japanese men virus in , Batchelet S, Moritz RL, Pellett S, Haugen BJ, FR, Blattner S, RL,BJ, Haugen Moritz Pellett S, Batchelet , a P

gonococcal urethritis in men. S men. in urethritis gonococcal posit - - aguchi Sasa S, w oh E, Namiki M. Pr oh E, Namiki M. Author manuscript; a

. K . Urease. In: Mobl In: . Urease. T

L ini LA, Dedent ini , H , y ff kami A, kami A, e elopes gram of ysiologyand Genetics. v ong ES, Hooton TM, Hooton CC,Hill TM, Mc ong ES, h n Uropathogenic Escherichia coli use d coli use Uropathogenic Escherichia 49:55 2003; Microbiol. urinary tract. Mol Mizo and papillom human urethral papillom human 21213011] in J Dis. 158:1098 1988; urethritis Infect men. nongonococcal of recurrent persistent or [PubMed: 3183419] e 16524923] P asymptomatic non 18842690] W Microbiol Spectr 382. Roesch PL, 382. Redford PL, Roesch 378. Shigehara K, K 378. Shigehara 379. 380. Marra 381. Mobl 377. Moi H, Reinton N, Moghaddam N, 377.Reinton Moi H, wis e Kline and L

Author Manuscript Author Manuscript Author Manuscript Author Manuscript Kline and Lewis Page 47

Describes Staphylococcus, Enterococcus, and Streptococcus as uropathogens, discusses :l> c polymicrobial urinary tract infection, the significance of polymicrobial growth upon urine ::r -0 culture, and the potential under-reporting of fastidious organisms and atypical Gram• positives as causes of urinary tract infection. Finally, this chapter summarizes current

literature regarding the microbiota of the urinary tract and discusses the potential role of urogenital microbiota in UTI susceptibility.

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Author Manuscript Author Manuscript Author Manuscript Author Manuscript Table 1

Genera of Gram-positive human urinary tract inhabitants and pathogens detected by culture-dependent and –independent techniques L and Kline

“culture negative” means specimens that did not reach the cutoff value, usually 105 CFU/ml urine in a clean catch specimen or 104 CFU/ml for collections by catheter or suprapubic aspiration.

e wis Culture-Dependent Culture-Independent Detection in Urinary Tract Clinical Reports

Female, Female, Female culture-negative, Male Male

Microbiol Spectr Microbiol culture culture nitrite and leukocyte esterase asymptomatic symptomatic Bladder/ Bacteremia Phylum Genus Kidney & Urethritis unknown positive negative or asymptomatic

infection Urosepsis urethral TUC CC,TUC CC TUC SPA urine urine swab

[319, 5–20% of 53 55

. [ , , 328 292 329 318 319 317 329 317 322 323 330 Author manuscript; Author Staphylococcus 47 [ ] [ , ] n/r [ , ] [ , ] [ ] – [ ] [ ] CAUTI [ ] 56] 324]

15–30% of 322 Enterococcus CAUTI 328 331 332 318 316 333 319 n/r n/r [ , 323 330 [ ] [ , ] [ ] [ , ] [ ] 323 [ ] [ ] [13, 115, 119] ]

1–2% of UTI [292, 318, [316, 318, [322– a Streptococcus 180 334 n/r 317 329 317 323 330 v 180 [ ] [ ] 329 319 [ , ] [ ] 324 [ ] [ ] ailable in PMC 2016 June 01. June 2016 in PMC ailable [ ] ] ] ]

[319, [230, 232, 237, [233–236, Aerococcus n/r 329[ ,335 ] [317 ] [318 , 319 ] [317 ] [317 ] 322 , [323 ] n/r 239] 278] 323]

Firmicutes [319, [292, 329, [316, 318, Anaerococcus n/r n/r n/r [333 ] n/r [317 ] 322 – [323 ] n/r 335] 319, 333] 324]

319 [ , Peptostreptococcus [321, 336]* [337] n/r [335] [333] [318, 319] n/r n/r 322, n/r n/r 324]

319[ , Peptoniphilus n/r [338] n/r [335] [333] [317–319] n/r n/r n/r n/r 322]

[319, [321, 339, [316–319, Lactobacillus n/r n/r [335 ] [333 ] [317 , 329 ] [317 ] 322 – [323 ] [330 ] 340] * 333] 324]

P

age 53 age

Culture-Dependent Culture-Independent Detection in Urinary Tract Clinical Reports L and Kline Female, Female, Female culture-negative, Male Male Bladder/ Bacteremia culture culture nitrite and leukocyte esterase asymptomatic symptomatic Phylum Genus Kidney & Urethritis unknown positive negative or asymptomatic

infection Urosepsis e

urethral wis TUC CC,TUC CC TUC SPA urine urine swab

[319, 317 318 Finegoldia n/r n/r n/r 335 [ , , 319 n/r 317 322 323 330 [ ] 333 [ ] [ ] – [ ] [ ] ] 324

Microbiol Spectr Microbiol ]

337 322 Veillonella 341 342 [ , n/r 335 317 n/r 292 329 n/r [ , 324 n/r [ , ] 341 [ ] [ ] [ , ] 323 [ ] ] ] [319, 343 323 . Gemella n/r n/r n/r n/r n/r n/r n/r 322 n/r [ ] , [ ]

Author manuscript; Author 323]

[319, [246–249, 344– [292, 329, [316, 318, Corynebacterium 350[ ] 351[ –353 ] n/r [317 , 329 ] [317 ] 322 , [323 ] n/r 349] 335] 319] 323]

155 261 262 a [ , , , 270 v [ , ailable in PMC 2016 June 01. June 2016 in PMC ailable 266, 267, 269, 292[ ,317 , Actinobaculum 275, 278, n/r [335] [317, 333] [318, 319] [317 ] [322 ] n/r n/r 272, 274, 276, 329] 355] 277, 354]

[293, [317, 322– Actinobacteria 307[ –309 , [316 , 318 , [319 , Gardnerella [285, 300]* 300, 303, [335 ] [333 ] 324, 329, [317] [323 ] n/r 357–359] 319, 333] 322] 356] 360]

[319, 317 319 292 317 Atopobium n/r n/r n/r 335 333 [ , , [ , , 317 322 323 361 [ ] [ ] 333 329 [ ] , [ ] [ ] ] ] 323, 361]

Actinomyces [362–366] [367] n/r [335] n/r [319] [292] n/r [322] n/r n/r

Bifidobacterium n/r n/r n/r [335] [333] n/r [292, 329] n/r n/r n/r [330]

[319, [358 , 372 – Mycoplasma [368–371] n/r n/r n/r n/r n/r n/r 322, [323] n/r 379] 323]

n/r = not reported, CAUTI = community acquired UTI,

P * 54 age Questionable clinical significance, CC = clean catch, TUC = transurethral catheter, SPA = suprapubic aspiration.