G Model IJID 2665 1–8 International Journal of Infectious Diseases xxx (2016) xxx–xxx Contents lists available at ScienceDirect International Journal of Infectious Diseases jou rnal homepage: www.elsevier.com/locate/ijid 1 2 Review 3 Morganella morganii, a non-negligent opportunistic pathogen 1 1 4 Q1 Hui Liu , Junmin Zhu , Qiwen Hu, Xiancai Rao * 5 Department of Microbiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China A R T I C L E I N F O A B S T R A C T Article history: Morganella morganii belongs to the tribe Proteeae of the Enterobacteriaceae family. This species is Received 2 December 2015 considered as an unusual opportunistic pathogen that mainly causes post-operative wound and urinary Received in revised form 31 March 2016 tract infections. However, certain clinical M. morganii isolates present resistance to multiple antibiotics Accepted 6 July 2016 by carrying various resistant genes (such as blaNDM-1, and qnrD1), thereby posing a serious challenge for Corresponding Editor: Eskild Petersen, clinical infection control. Moreover, virulence evolution makes M. morganii an important pathogen. Aarhus, Denmark Accumulated data have demonstrated that M. morganii can cause various infections, such as sepsis, abscess, purple urine bag syndrome, chorioamnionitis, and cellulitis. This bacterium often results in a Keywords: high mortality rate in patients with some infections. M. morganii is considered as a non-negligent Morganella morganii opportunistic pathogen because of the increased levels of resistance and virulence. In this review, we epidemiology summarized the epidemiology of M. morganii, particularly on its resistance profile and resistant genes, as resistant genes well as the disease spectrum and risk factors for its infection. disease spectrum ß 2016 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. risk factors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/). 6 7 for urease production and presence of phenylalanine deaminase. 28 8 1. Introduction M. morganii is widely distributed in nature. This bacterium is 29 commonly found in the environment and intestinal tracts of 30 9 Q2 Morganella morganii is a facultative anaerobic rod Gram- 7 humans, mammals, and reptiles as part of the normal flora. The 31 10 negative enteric bacterium, which was first isolated in 1906 by 1 drug resistance of M. morganii is increasing in recent years, and this 32 11 Morgan et al. from a pediatric fecal culture. The genome size of M. 8,9 resistance is mainly introduced via extra genetic and mobile 33 12 morganii is about 4,000,000 bp, and the number of its protein- 2 10,11 elements. The infections caused by multidrug-resistant (MDR) 34 13 coding sequences (CDSs) is about 4,000. M. morganii was formerly 3 or even the extensively drug-resistant (XDR) M. morganii often 35 14 classified as Proteus morganii and later assigned to the genus 12,13 result in clinical treatment failure. Generally, M. morganii can 36 15 Morganella, which belongs to the tribe Proteeae of the Enterobacter- produce virulence factors, such as urease, hemolysins, and 37 16 iaceae family on the basis of DNA–DNA hybridization determina- 4 lipopolysaccharide (LPS); these virulence factors pose M. morganii 38 17 tions. Although members of the tribe Proteeae, including Proteus, an opportunistic pathogen that mainly causes wound and urinary 39 18 Providencia and Morganella, share homologous genes acquired from 14–16 tract infections. Comparative genome analysis revealed 40 19 horizontal gene transfer via mobile transposition or conjugative several pathogenicity-related genes, and novel genes carried by 41 20 integration, the overall G+C contents in the genomes of other M. morganii genome are not found in the genomes of other Proteeae 42 21 Proteeae members range from 39% to 43%, which are lower than that members, which may provide important information concerning 43 22 of the M. morganii (51%); therefore, the G+C contents provides 5 17 the virulence and fitness determinants in M. morganii. The 44 23 genetic evidence for distinguishing M. morganii from other species. disease spectrum of M. morganii infection varies and is changeable 45 24 The genus Morganella currently consists of a single species (M. 6 according to its virulence evolution. This review aims to 46 25 morganii) with two subspecies, namely, morganii and sibonii. summarize the epidemiology of M. morganii, focus on its resistance 47 26 Biologically, M. morganii is a motile, non-lactose fermenting profile and resistant genes, and discuss its disease spectrum and 48 27 bacterium, which shares with the Proteus members on the capacity risk factors for infection. 49 * Corresponding author. Department of Microbiology, Third Military Medical # 2. Epidemiology of M. morganii 50 University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, China. Tel.: +86-23-68752240; fax:+86-23-68752240. As a member of the family Enterobacteriaceae, M. morganii is 51 E-mail address: [email protected] (X. Rao). 1 18 Drs Liu and Zhu made an equal contribution to this study considered as a rare cause of nosocomial infection. Farmer et al. 52 http://dx.doi.org/10.1016/j.ijid.2016.07.006 1201-9712/ß 2016 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Liu H, et al. Morganella morganii, a non-negligent opportunistic pathogen. Int J Infect Dis (2016), http:// dx.doi.org/10.1016/j.ijid.2016.07.006 G Model IJID 2665 1–8 2 H. Liu et al. / International Journal of Infectious Diseases xxx (2016) xxx–xxx 53 classified the bacteria of Enterobacteriaceae among 11 levels cell obtains the ability to resist the activity of a particular 117 54 according to the relative frequency of a certain bacterium isolated antimicrobial agent to which it was susceptible previously. This 118 55 from the clinical specimen. The relative frequency increases from 0 phenomenon can result from the acquisition of foreign resistance 119 56 (not known to occur) to 10 (most common), in which that of M. genes that are horizontally transferred between different strains or 120 57 morganii is 4, i.e., an opportunistic pathogen that causes rare even species via conjugation, or/and from the mutation in certain 121 58 infection. genes involved in normal physiological processes and cellular 122 59 Originally, M. morganii was thought to be a cause of summer structures. However, adaptive resistance happens when the 123 1 60 diarrhea and considered to be a very unimportant pathogen. This bacterial population is subjected to gradual antibiotic increases; 124 61 bacterium was first found to be a cause of urinary tract infection in this resistance is characterized by a rapid emergence of resistance 125 62 1939. In the 1970s, M. morganii was shown to be a primary cause of and reversibility to the normal phenotype when the antibiotic is 126 32 63 nosocomial infection in adults and a rare cause of bacteremia. removed. Adaptive resistance may require epigenetic inheri- 127 19 64 Adler et al. isolated six M. morganii strains from 71 cases of tance and modification of gene expression patterns in the 128 65 Proteusbacillus vulgaris bacteremia through investigating the particular bacterial population. 129 66 characteristics of P. vulgaris infections and epidemiology in a All three kinds of resistances may occur in a particular bacterial 130 67 general hospital. In the early 1980s, Tucci and Isenberg reported species. M. morganii has intrinsic resistance to oxacillin, ampicillin, 131 68 13 M. morganii infections scattered over four services and five amoxicillin, most of the first- and second-generation cephalospor- 132 69 floors of a hospital; this outbreak was eventually resolved when ins, macrolides, lincosamides, glycopeptides, fosfomycin, fusidic 133 14 70 strict aseptic techniques, i.e., hand washing, were reinforced. acid, and colistin; this pathogen is also normally sensitive to 134 71 Following that incident, M. morganii has been identified as a aztreonam, aminoglycosides, antipseudomonal penicillins, third- 135 72 significant cause of nosocomial infection, but recognized as an and fourth-generation cephalosporins, carbapenems, quinolones, 136 33 73 increasingly important pathogen in recent years. Over a six-year trimethoprim/ sulfamethoxazole, and chloramphenicol. A 137 74 period (2006–2011), samples from all patients who presented unique biochemical character of M. morganii is that this organism 138 75 symptoms of Gram-negative bacterial infections at Changhua has the capability for extracellular biosynthesis of crystalline silver 139 76 Christian Hospital, Taiwan, were collected. Of the 82,861 samples, nanoparticles, which was found independent of environmental 140 34 77 1,219 (1.47%) are positive for M. morganii, which is the ninth changes. Three chromosomal gene homologues (silE, silP and silS) 141 78 prevalent cause of clinical infections in patients at the said identified in M. morganii were characterized to be responsible for 142 17 + 79 hospital. In addition to Taiwan, other regions including Japan, the biosynthesis of silver nanoparticles in the presence of Ag ions, 143 35 80 USA, and Spain are also the most frequent areas with reported M. as well as the silver-resistant phenotype of the strain. 144 81 morganii-associated infections. However, the M. morganii-associ- Nevertheless, the acquired resistance is increasingly observed in 145 82 ated case reports are scattered and often present in immunocom- M. morganii. According to the recent data from the SENTRY 146 12,20–26 83 promised patients. No link exists between case reported antimicrobial resistance surveillance program, M. morganii ranks 147 84 areas and economic status, sanitary condition, natural environ- 12th among the Gram-negative organisms that cause bloodstream 148 36 85 ment, and population mobility.