Dataset Information

Short-term genome stability of serial Clostridium difficile ribotype 027 isolates in an experimental gut model and recurrent human disease.

ABSTRACT:

Background

Clostridium difficile whole genome sequencing has the potential to identify related isolates, even among otherwise indistinguishable strains, but interpretation depends on understanding genomic variation within isolates and individuals.

Methods

Serial isolates from two scenarios were whole genome sequenced. Firstly, 62 isolates from 29 timepoints from three in vitro gut models, inoculated with a NAP1/027 strain. Secondly, 122 isolates from 44 patients (2-8 samples/patient) with mostly recurrent/on-going symptomatic NAP-1/027 C. difficile infection. Reference-based mapping was used to identify single nucleotide variants (SNVs).

Results

Across three gut model inductions, two with antibiotic treatment, total 137 days, only two new SNVs became established. Pre-existing minority SNVs became dominant in two models. Several SNVs were detected, only present in the minority of colonies at one/two timepoints. The median (inter-quartile range) [range] time between patients' first and last samples was 60 (29.5-118.5) [0-561] days. Within-patient C. difficile evolution was 0.45 SNVs/called genome/year (95%CI 0.00-1.28) and within-host diversity was 0.28 SNVs/called genome (0.05-0.53). 26/28 gut model and patient SNVs were non-synonymous, affecting a range of gene targets.

Conclusions

The consistency of whole genome sequencing data from gut model C. difficile isolates, and the high stability of genomic sequences in isolates from patients, supports the use of whole genome sequencing in detailed transmission investigations.

SUBMITTER: Eyre DW

PROVIDER: S-EPMC3655144 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Short-term genome stability of serial Clostridium difficile ribotype 027 isolates in an experimental gut model and recurrent human disease.

Eyre David W DW Walker A Sarah AS Freeman Jane J Baines Simon D SD Fawley Warren N WN Chilton Caroline H CH Griffiths David D Vaughan Alison A Crook Derrick W DW Peto Tim E A TE Wilcox Mark H MH

PloS one 20130515 5

<h4>Background</h4>Clostridium difficile whole genome sequencing has the potential to identify related isolates, even among otherwise indistinguishable strains, but interpretation depends on understanding genomic variation within isolates and individuals.<h4>Methods</h4>Serial isolates from two scenarios were whole genome sequenced. Firstly, 62 isolates from 29 timepoints from three in vitro gut models, inoculated with a NAP1/027 strain. Secondly, 122 isolates from 44 patients (2-8 samples/patie ...[more]

PMID: 23691061

Similar Datasets

Project description:BackgroundClostridium difficile infection (CDI) is an emerging healthcare problem in the world. The purpose of this study was to perform a systematic epidemiological research of CDI in Tongji hospital, the central of China.MethodsStool samples from hospitalized adults suspected of CDI were enrolled. The diagnosis of CDI were based on the combination of clinical symptoms and laboratory results. Clinical features of CDI and non-CDI patients were compared by appropriate statistical tests to determine the risk factors of CDI. Multilocus sequence typing (MLST) was employed for molecular epidemiological analysis. Susceptibility testing and relevant antimicrobial agent resistance genes were performed as well.ResultsFrom June 2016 to September 2017, 839 hospitalized adults were enrolled. Among them, 107 (12.8%, 107/839) patients were C. difficile culture positive, and 73 (8.7%, 73/839) were infected with toxigenic C. difficile (TCD), with tcdA + tcdB+ strains accounting for 90.4% (66/73) and tcdA-tcdB+ for 9.6% (7/73). Meanwhile, two TCD strains were binary toxin positive and one of them was finally identified as CD027. Severe symptoms were observed in these two cases. Multivariate analysis indicated antibiotic exposure (p = 0.001, OR = 5.035) and kidney disease (p = 0.015, OR = 8.329) significantly increased the risk of CDI. Phylogenetic tree analysis demonstrated 21 different STs, including one new ST (ST467); and the most dominant type was ST54 (35.6%, 26/73). Multidrug-resistant (MDR) TCD were 53.4% (39/73); resistance to ciprofloxacin, erythromycin, and clindamycin were > 50%. Other antibiotics showed relative efficiency and all strains were susceptible to metronidazole and vancomycin. All moxifloxacin-resistant isolates carried a mutation in GyrA (Thr82 → Ile), with one both having mutation in GyrB (Ser366 → Ala).ConclusionsKnowledge of epidemiological information for CDI is limited in China. Our finding indicated tcdA + tcdB+ C. difficile strains were the dominant for CDI in our hospital. Significant risk factors for CDI in our setting appeared to be antibiotic exposure and kidney disease. Metronidazole and vancomycin were still effective for CDI. Although no outbreak was observed, the first isolation of CD027 in center China implied the potential spread of this hypervirulent clone. Further studies are needed to enhance our understanding of the epidemiology of CDI in China.

Dataset Information

Short-term genome stability of serial Clostridium difficile ribotype 027 isolates in an experimental gut model and recurrent human disease.

Background

Methods

Results

Conclusions

Publications

Short-term genome stability of serial Clostridium difficile ribotype 027 isolates in an experimental gut model and recurrent human disease.

Similar Datasets

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