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The genome of Clostridium difficile 5.3.

ABSTRACT: BACKGROUND:Clostridium difficile is the leading cause of infectious diarrhea in humans and responsible for large outbreaks of enteritis in neonatal pigs in both North America and Europe. Disease caused by C. difficile typically occurs during antibiotic therapy and its emergence over the past 40 years is linked with the widespread use of broad-spectrum antibiotics in both human and veterinary medicine. RESULTS:We sequenced the genome of Clostridium difficile 5.3 using the Illumina Nextera XT and MiSeq technologies. Assembly of the sequence data reconstructed a 4,009,318 bp genome in 27 scaffolds with an N50 of 786 kbp. The genome has extensive similarity to other sequenced C. difficile genomes, but also has several genes that are potentially related to virulence and pathogenicity that are not present in the reference C. difficile strain. CONCLUSION:Genome sequencing of human and animal isolates is needed to understand the molecular events driving the emergence of C. difficile as a gastrointestinal pathogen of humans and food animals and to better define its zoonotic potential.

SUBMITTER: Darling AE

PROVIDER: S-EPMC4234979 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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The genome of Clostridium difficile 5.3.

Darling Aaron E AE Worden Paul P Chapman Toni A TA Roy Chowdhury Piklu P Charles Ian G IG Djordjevic Steven P SP

Gut pathogens 20140224 1

<h4>Background</h4>Clostridium difficile is the leading cause of infectious diarrhea in humans and responsible for large outbreaks of enteritis in neonatal pigs in both North America and Europe. Disease caused by C. difficile typically occurs during antibiotic therapy and its emergence over the past 40 years is linked with the widespread use of broad-spectrum antibiotics in both human and veterinary medicine.<h4>Results</h4>We sequenced the genome of Clostridium difficile 5.3 using the Illumina ...[more]

PMID: 24565059

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Project description:Clostridium difficile is a spore-forming anaerobic bacterium that causes colitis in patients with disrupted colonic microbiota. While some individuals are asymptomatic C. difficile carriers, symptomatic disease ranges from mild diarrhea to potentially lethal toxic megacolon. The wide disease spectrum has been attributed to the infected host's age, underlying diseases, immune status, and microbiome composition. However, strain-specific differences in C. difficile virulence have also been implicated in determining colitis severity. Because patients infected with C. difficile are unique in terms of medical history, microbiome composition, and immune competence, determining the relative contribution of C. difficile virulence to disease severity has been challenging, and conclusions regarding the virulence of specific strains have been inconsistent. To address this, we used a mouse model to test 33 clinical C. difficile strains isolated from patients with disease severities ranging from asymptomatic carriage to severe colitis, and we determined their relative in vivo virulence in genetically identical, antibiotic-pretreated mice. We found that murine infections with C. difficile clade 2 strains (including multilocus sequence type 1/ribotype 027) were associated with higher lethality and that C. difficile strains associated with greater human disease severity caused more severe disease in mice. While toxin production was not strongly correlated with in vivo colonic pathology, the ability of C. difficile strains to grow in the presence of secondary bile acids was associated with greater disease severity. Whole-genome sequencing and identification of core and accessory genes identified a subset of accessory genes that distinguish high-virulence from lower-virulence C. difficile strains.IMPORTANCEClostridium difficile is an important cause of hospital-associated intestinal infections, and recent years have seen an increase in the number and severity of cases in the United States. A patient's antibiotic history, immune status, and medical comorbidities determine, in part, the severity of C. difficile infection. The relative virulence of different clinical C. difficile strains, although postulated to determine disease severity in patients, has been more difficult to consistently associate with mild versus severe colitis. We tested 33 distinct clinical C. difficile isolates for their ability to cause disease in genetically identical mice and found that C. difficile strains belonging to clade 2 were associated with higher mortality. Differences in survival were not attributed to differences in toxin production but likely resulted from the distinct gene content in the various clinical isolates.

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The genome of Clostridium difficile 5.3.

Publications

The genome of Clostridium difficile 5.3.

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