98 DIC 2014 NÚMERO 58 Why isitimportant? What dowedo? Seamus O’Brien,ChrisConnolly. Sudeepta Chakravarty, Kevin,MiguelValvano, Bernadette LauraBurns, Fondo:TinaSchmidt,LucieKalferstova,AnnaHanuszkiewicz, Foto degrupo.Alfrente, deizquierda aderecha,Yasmine Fathy, KinaPatel,JanetTorres, GonzaloPradenas,AmyFord, CristobalMujica, http://publish.uwo.ca/~mvalvano/index.html of ourresearch program. flexneri are the model organisms weuseindifferent aspects our main model organisms tostudy the pathogenicity of ria (Bcc)and Burkholderiacenocepaciainparticular are immunosuppressed. eases, cancer, and organ transplantation, butwho become most from advancements inthe treatment of genetic dis- human health, especially tothose patients who benefit cepacia, negative at the molecular level. structural biology tounderstand the pathogenesis of Gram- using molecular genetics, biochemistry, cellbiology, and r MICROBIOLOGÍA MOLECULA Centre for Infection andImmunity,Queen's University Belfast, Belfast. UnitedKingdom Opportunistic infections poseasignificant threat to Our research involvesaninterdisciplinary approach Pathogenesis Research Group , Miguel A.Valvano, MwD. Professor of Microbiology andInfectious Diseases Microbial Biochemistryand Burkholderia cepaciacomplex bacte - enterica,and Shigella Burkholderia ceno- effect of these infections insusceptiblepatients. we hope to find novel ways to prevent or ameliorate the ically usefulantimicrobials. Therefore, throughout research given the extraordinary resistance of these bacteria toclin- by these microorganisms, which are verydifficult totreat patients commonly sufferfrom lung and airwaysinfections cystic fibrosis and chronic granulomatous disease. These for children and young adults withgenetic conditions like opportunistic bacteria. Bccbacteria are amajor health risk host defensive mechanisms such asthe serumcomplement to avariety of antibiotics and they canbeeasilykilledby teria withdefects inthe LPS molecule are more sensitive structural component of the bacterial outermembrane. Bac- the surface of Gram-negative bacteria thatisalsoacritical charide (LPS)isacomplex glycolipid molecule locatedon ticularly endemic incertainpartsof the world. Lipopolysac- Shigella are alsoimportant human , which are par- Enteric bacteria such asEscherichiacoli, [email protected] Salmonella, and DIC 2014 99

(2013). The(2013). NÚMERO 58 MICROBIOLOGÍA MOLECULARMICROBIOLOGÍA . J Bacteriol 194:2646-2657. Caulobacter crescentus. J Bacteriol and Escherichia coli and - mul Burkholderia cenocepacia targets system of VI secretion Type the and actin cytoskeleton the disrupting GTPases family Rho tiple Cell Microbiol in macrophages. complex NADPH oxidase of assembly 14:255-273. of identification topology and MA. (2010). Membrane A y Valvano from translocase Wzx O-antigen in the residues acid amino critical 192:6160-6171. Escherichia coli O157:H4. J Bacteriol - dela the for is required phosphatase tyrosine a non-functional ding in macrophages. vacuoles bacteria-containing the of yed maturation 160:1332-1345. Microbiology Burkholderia cenocepacia and of manipulation genetic for method Host- In bacteria. Gram-negative resistant antibiotic multi other pp. 311-327. Edited Protocols, and Methods interactions: bacteria Press. A y Callaghan D O: Human by Vergunst Rev (in press). Clin Microbiol of clarity. need field in an emerging MA. (2014). Identification y Valvano GA PN, Lajoie A, Moynagh ro and system in Burkholderia cenocepacia glycosylation flagellin the of innate human of to evasion glycosylated flagellin of contribution the 289:19231-19244. Chem J Biol responses. immune synthesis cell wall peptidoglycan for is essential (MviN) homolog 24:564-576. Glycobiology viability. bacterial and Burkholderia the of MA. (2014). Elucidation mons RE y Valvano for functions pathway uncovers biosynthesis cenocepacia hopanoid - Micro Environ bacteria. in hopanoid-producing proteins conserved 10.1111/1462-2920.12509. doi: biol is a global regulator AtsR hybrid kinase Burkholderia cenocepacia sensor 15:372-385. Microbiol Environ signalling. quorum-sensing modulating - identi pathway and phosphorelay kinase sensor hybrid AtsR the of regulator in Burkholderia cenocepacia. J Biol response of its fication 288:30473-30484. Chem intrinsic and export lipopolysaccharide for is essential rabinose in Burkholderia cenocepacia. Mol resistance peptide antimicrobial 85:962-974. Microbiol UDP- of characterization Functional MA. (2012). MA y Valvano nards of Transferases Glucose-1-Phosphate Glucose:Undecaprenyl-Phosphate survival and in bacterial survival in the rat model of of in the rat model in bacterial survival survival and infection? chronic lung - protect essen mechanisms How do bacterial to be that are deemed metabolic pathways tial bacterial includ- environments, adaptation to different critical for ing the lung and airways? our spe- available for not tools are genetic Sometimes cific research needs. Therefore, we place special effort in in effort we place special Therefore, needs. research cific those or modifying reagents tools and new developing our lab has con- In particular, needs. available to our own Bcc bacteria. tools to handle molecular tributed novel (2012). The MA. (2012). The DF y Valvano AM, Aubert R, Skeldon Rosales-Reyes Roa Rosales A, M, Hanuszkiewicz CL, Li B, Lung M, Yang Marolda Reciente Bibliografía - enco gene MA. (2014). A Burkholderia cenocepacia A y Valvano Andrade deletion MA. (2014). A markerless Hamad MA y Valvano DF, Aubert heteroresistance: MA. (2014). Antimicrobial OM y Valvano El-Halfawy Molina- AR, Moll H, Rosales Humphries F, P, Pittock A, Hanuszkiewicz MurJ MA. (2014). A Burkholderia cenocepacia Mohamed YF y Valvano MA, Sum- Hamad MA, Bain KL, Bernards PV, Schmerk CL, Welander MA. Valvano y PA Sokol MA, Hamad EP, O’Grady DF, Aubert MA. (2013). Characterization DF y Valvano M, Aubert Khodai-Kalaki - MA. (2012). Aminoa A y Valvano Molinaro F, Hamad MA, Di Lorenzo Ber- GG, Brun YV, A, Hardy XB, Hanuszkiewicz Fernandez E, KB, Toh Patel , and and Salmonella, E. coli, E. , and Shigella Salmonella enterica, and How does B. cenocepacia adapt to various environments How does B. including macrophage and epithelial cells? in intracellular regulators stress of the roles What are We discovered several master regulators that respond to respond that regulators master several discovered We How does intracellular B. cenocepacia delay phagosome How does intracellular B. maturation and phagosomal acidification? B. in system 6-secretion type novel a of the role is What cenocepacia intracellular survival? cenocepacia affect the assem- How does intracellular B. macrophage NADPH oxidase? the bly of We discovered that Bcc bacteria survive intracellularly intracellularly survive bacteria Bcc that discovered We How LPS components are synthesized? the translocation What are the mechanistic bases of across the intermediates O-antigen LPS biosynthesis of plasma membrane? antimicrobial of How Bcc bacteria can survive the attack cationic peptides and other antibiotics? We discovered that genetic ablation of LPS synthesis LPS synthesis of ablation that genetic discovered We different types of stress. Mutations in the genes encoding these encoding genes in the Mutations stress. types of different cenocepacia to survive within B. ability of impair the regulators lung chronic of model animal also in the and macrophages - defens bacterial have observed that antioxidant We infection. learn: to want we Now survival. intracellular for critical are es in free-living amoebae and macrophages by altering the the altering by macrophages and amoebae in free-living has led to this research and phagosome, the of maturation the for a reservoir cells become that these hypothesis the host. in the bacteria these of dissemination and persistence ceno- system in B. secretory a novel discovered have also We of cytoskeleton the alter to appears that VI) cepacia (type in an ani- infection for is required and infected macrophages to learn: we want Now infection. lung chronic of model mal . Now we want to learn: we want Shigella. Now or chemical inhibitors of certain LPS biosynthesis enzymes enzymes certain LPS biosynthesis inhibitors of or chemical facilitate and outer membrane bacterial the can «weaken» antimicrobial and antibiotics conventional of entry the Bcc bac- other and cenocepacia in B. especially peptides, on proteins studies detailed have also conducted We teria. O and oligosaccharide core of synthesis the for required components These LPS molecules. the of moieties antigen of virulence the for crucial are les of key questions Examples of key questions investigate we currently and antimicrobial peptides. Therefore, by understanding how how by understanding Therefore, peptides. antimicrobial and surface cell bacterial on the assembled and LPS is made the with this will interfere inhibitors that to design we hope Also, antimicrobials. novel as useful be may which process, at vari- biosynthesis at ways to alter LPS looking we are outer the of permeability overall the ous levels to increase What peptides. antimicrobial and antibiotics membrane to , we learn in Escherichia coli . to Burkholderia cenocepacia is also applied flexneri