Clinical Clostridium difficile: Clonality and Pathogenicity Locus Diversity

被引:138
作者
Dingle, Kate E. [1 ,2 ]
Griffiths, David [2 ,3 ]
Didelot, Xavier [4 ]
Evans, Jessica [2 ,3 ]
Vaughan, Alison [2 ,3 ]
Kachrimanidou, Melina [2 ,3 ]
Stoesser, Nicole [2 ,3 ]
Jolley, Keith A. [5 ]
Golubchik, Tanya [4 ]
Harding, Rosalind M. [5 ]
Peto, Tim E. [2 ,3 ]
Fawley, Warren [6 ]
Walker, A. Sarah [2 ,3 ]
Wilcox, Mark [6 ,7 ]
Crook, Derrick W. [2 ,3 ]
机构
[1] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, England
[2] John Radcliffe Hosp, Natl Inst Hlth Res, Oxford Biomed Res Ctr Programme, Oxford OX3 9DU, England
[3] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England
[4] Univ Oxford, Dept Stat, Oxford OX1 3TG, England
[5] Univ Oxford, Dept Zool, Oxford OX1 3PS, England
[6] Gen Infirm, Dept Microbiol, Old Med Sch, Leeds LS1 3EX, W Yorkshire, England
[7] Univ Leeds, Dept Microbiol, Inst Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England
来源
PLOS ONE | 2011年 / 6卷 / 05期
基金
英国惠康基金;
关键词
TOXIN-B; INCREASED SPORULATION; HYPERVIRULENT STRAIN; SEQUENCE-ANALYSIS; PCR; EPIDEMIC; INFECTION; TCDC; MICROEVOLUTION; TRANSCRIPTION;
D O I
10.1371/journal.pone.0019993
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Clostridium difficile infection (CDI) is an important cause of mortality and morbidity in healthcare settings. The major virulence determinants are large clostridial toxins, toxin A (tcdA) and toxin B (tcdB), encoded within the pathogenicity locus (PaLoc). Isolates vary in pathogenicity from hypervirulent PCR-ribotypes 027 and 078 with high mortality, to benign non-toxigenic strains carried asymptomatically. The relative pathogenicity of most toxigenic genotypes is still unclear, but may be influenced by PaLoc genetic variant. This is the largest study of C. difficile molecular epidemiology performed to date, in which a representative collection of recent isolates (n = 1290) from patients with CDI in Oxfordshire, UK, was genotyped by multilocus sequence typing. The population structure was described using NeighborNet and ClonalFrame. Sequence variation within toxin B (tcdB) and its negative regulator (tcdC), was mapped onto the population structure. The 69 Sequence Types (ST) showed evidence for homologous recombination with an effect on genetic diversification four times lower than mutation. Five previously recognised genetic groups or clades persisted, designated 1 to 5, each having a strikingly congruent association with tcdB and tcdC variants. Hypervirulent ST-11 (078) was the only member of clade 5, which was divergent from the other four clades within the MLST loci. However, it was closely related to the other clades within the tcdB and tcdC loci. ST-11 (078) may represent a divergent formerly non-toxigenic strain that acquired the PaLoc (at least) by genetic recombination. This study focused on human clinical isolates collected from a single geographic location, to achieve a uniquely high density of sampling. It sets a baseline of MLST data for future comparative studies investigating genotype virulence potential (using clinical severity data for these isolates), possible reservoirs of human CDI, and the evolutionary origins of hypervirulent strains.
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页数:10
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