Comparative Phylogenomics of Clostridium Difficile Reveals Clade Specificity and Microevolution of Hypervirulent Strains

Overview

Journal J Bacteriol

Publisher American Society for Microbiology

Specialty Microbiology

Date 2006 Oct 4

PMID 17015669

Citations 113

Authors

R A Stabler

D N Gerding

J G Songer

D Drudy

J S Brazier

H T Trinh

A A Witney

J Hinds

B W Wren

Affiliations

Soon will be listed here.

Abstract

Clostridium difficile is the most frequent cause of nosocomial diarrhea worldwide, and recent reports suggested the emergence of a hypervirulent strain in North America and Europe. In this study, we applied comparative phylogenomics (whole-genome comparisons using DNA microarrays combined with Bayesian phylogenies) to model the phylogeny of C. difficile, including 75 diverse isolates comprising hypervirulent, toxin-variable, and animal strains. The analysis identified four distinct statistically supported clusters comprising a hypervirulent clade, a toxin A(-) B(+) clade, and two clades with human and animal isolates. Genetic differences among clades revealed several genetic islands relating to virulence and niche adaptation, including antibiotic resistance, motility, adhesion, and enteric metabolism. Only 19.7% of genes were shared by all strains, confirming that this enteric species readily undergoes genetic exchange. This study has provided insight into the possible origins of C. difficile and its evolution that may have implications in disease control strategies.

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References

Hinchliffe S, Isherwood K, Stabler R, Prentice M, Rakin A, Nichols R . Application of DNA microarrays to study the evolutionary genomics of Yersinia pestis and Yersinia pseudotuberculosis. Genome Res. 2003; 13(9):2018-29. PMC: 403674. DOI: 10.1101/gr.1507303. View

Fawley W, Freeman J, Wilcox M . Evidence to support the existence of subgroups within the UK epidemic Clostridium difficile strain (PCR ribotype 1). J Hosp Infect. 2003; 54(1):74-7. DOI: 10.1016/s0195-6701(03)00079-3. View

He G, Kuroda T, Mima T, Morita Y, Mizushima T, Tsuchiya T . An H(+)-coupled multidrug efflux pump, PmpM, a member of the MATE family of transporters, from Pseudomonas aeruginosa. J Bacteriol. 2003; 186(1):262-5. PMC: 303449. DOI: 10.1128/JB.186.1.262-265.2004. View

Toyokawa M, Ueda A, Tsukamoto H, Nishi I, Horikawa M, Sunada A . Pseudomembranous colitis caused by toxin A-negative/toxin B-positive variant strain of Clostridium difficile. J Infect Chemother. 2003; 9(4):351-4. DOI: 10.1007/s10156-003-0269-z. View

Lemee L, Dhalluin A, Pestel-Caron M, Lemeland J, Pons J . Multilocus sequence typing analysis of human and animal Clostridium difficile isolates of various toxigenic types. J Clin Microbiol. 2004; 42(6):2609-17. PMC: 427854. DOI: 10.1128/JCM.42.6.2609-2617.2004. View

Wust J, SULLIVAN N, Hardegger U, Wilkins T . Investigation of an outbreak of antibiotic-associated colitis by various typing methods. J Clin Microbiol. 1982; 16(6):1096-101. PMC: 272546. DOI: 10.1128/jcm.16.6.1096-1101.1982. View

Clabots C, Johnson S, Bettin K, Mathie P, Mulligan M, Schaberg D . Development of a rapid and efficient restriction endonuclease analysis typing system for Clostridium difficile and correlation with other typing systems. J Clin Microbiol. 1993; 31(7):1870-5. PMC: 265648. DOI: 10.1128/jcm.31.7.1870-1875.1993. View

Johnson S, Gerding D . Clostridium difficile--associated diarrhea. Clin Infect Dis. 1998; 26(5):1027-34; quiz 1035-6. DOI: 10.1086/520276. View

Rupnik M, Avesani V, Janc M, von Eichel-Streiber C, Delmee M . A novel toxinotyping scheme and correlation of toxinotypes with serogroups of Clostridium difficile isolates. J Clin Microbiol. 1998; 36(8):2240-7. PMC: 105025. DOI: 10.1128/JCM.36.8.2240-2247.1998. View

10.

Chaves-Olarte E, Low P, Freer E, Norlin T, Weidmann M, von Eichel-Streiber C . A novel cytotoxin from Clostridium difficile serogroup F is a functional hybrid between two other large clostridial cytotoxins. J Biol Chem. 1999; 274(16):11046-52. DOI: 10.1074/jbc.274.16.11046. View

11.

Rahmati A, Gal M, Northey G, Brazier J . Subtyping of Clostridium difficile polymerase chain reaction (PCR) ribotype 001 by repetitive extragenic palindromic PCR genomic fingerprinting. J Hosp Infect. 2005; 60(1):56-60. DOI: 10.1016/j.jhin.2004.09.034. View

12.

Songer J . The emergence of Clostridium difficile as a pathogen of food animals. Anim Health Res Rev. 2005; 5(2):321-6. DOI: 10.1079/ahr200492. View

13.

Dorrell N, Hinchliffe S, Wren B . Comparative phylogenomics of pathogenic bacteria by microarray analysis. Curr Opin Microbiol. 2005; 8(5):620-6. PMC: 7108221. DOI: 10.1016/j.mib.2005.08.012. View

14.

Warny M, Pepin J, Fang A, Killgore G, Thompson A, Brazier J . Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet. 2005; 366(9491):1079-84. DOI: 10.1016/S0140-6736(05)67420-X. View

15.

Kuijper E, Debast S, van Kregten E, Vaessen N, Notermans D, van den Broek P . [Clostridium difficile ribotype 027, toxinotype III in The Netherlands]. Ned Tijdschr Geneeskd. 2005; 149(38):2087-9. View

16.

Pepin J, Saheb N, Coulombe M, Alary M, Corriveau M, Authier S . Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis. 2005; 41(9):1254-60. DOI: 10.1086/496986. View

17.

Gal M, Northey G, Brazier J . A modified pulsed-field gel electrophoresis (PFGE) protocol for subtyping previously non-PFGE typeable isolates of Clostridium difficile polymerase chain reaction ribotype 001. J Hosp Infect. 2005; 61(3):231-6. DOI: 10.1016/j.jhin.2005.01.017. View

18.

Champion O, Gaunt M, Gundogdu O, Elmi A, Witney A, Hinds J . Comparative phylogenomics of the food-borne pathogen Campylobacter jejuni reveals genetic markers predictive of infection source. Proc Natl Acad Sci U S A. 2005; 102(44):16043-8. PMC: 1276044. DOI: 10.1073/pnas.0503252102. View

19.

Loo V, Poirier L, Miller M, Oughton M, Libman M, Michaud S . A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005; 353(23):2442-9. DOI: 10.1056/NEJMoa051639. View

20.

McDonald L, Killgore G, Thompson A, Owens Jr R, Kazakova S, Sambol S . An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005; 353(23):2433-41. DOI: 10.1056/NEJMoa051590. View