Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium

Stabler, Richard A.; He, Miaoxia; Dawson, Lisa F.; Martin, Melissa J.; Valiente, Esmeralda; Corton, Craig; Lawley, Trevor D.; Sebaihia, Mohammed; Quail, Michael A.; Rose, Graham; Gerding, Dale N.; Gibert, Maryse; Popoff, Michel R.; Parkhill, Julian; Dougan, Gordon; Wren, Brendan W.

doi:10.1186/gb-2009-10-9-r102

Cited by 425 publications

(496 citation statements)

References 69 publications

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“…630 (RT 012), mobile elements accounted for ~10% of the genome and included a plasmid, prophages, transposons, IStrons, genomic islands, CRISPRs and a skin element (Sebaihia et al, 2006). This has remained consistent in the annotated genomes of other strains published since, including M120 (clade 5), and R20291 (clade 2) (He et al, 2010;Stabler et al, 2009). …”

Section: Accepted Manuscriptmentioning

confidence: 64%

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology

Elliott

Androga

Knight

et al. 2017

Infection, Genetics and Evolution

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Over the recent decades, Clostridium difficile infection (CDI) has emerged as a global public health threat. Despite growing attention, C. difficile remains a poorly understood pathogen, however, the exquisite sensitivity offered by next generation sequencing (NGS) technology has enabled analysis of the genome of C. difficile, giving us access to massive genomic data on factors such as virulence, evolution, and genetic relatedness within C. difficile groups. NGS has also demonstrated excellence in investigations of outbreaks and disease transmission, in both small and large-scale applications. This review summarizes the molecular epidemiology, evolution, and phylogeny of C. difficile, one of the most important pathogens worldwide in the current antibiotic resistance era.

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Section: Accepted Manuscriptmentioning

confidence: 64%

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology

Elliott

Androga

Knight

et al. 2017

Infection, Genetics and Evolution

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“…It was reported that TcdA is relatively well conserved, while TcdB has much variability, 38,39 especially the RBD region. 38 The N terminus encompassing the GTD and CPD domains is more conserved between historical and epidemic strains.…”

Section: Discussionmentioning

confidence: 99%

A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity againstClostridium difficileinfection in mice and hamsters

Wang

Yan

Kim

et al. 2015

Human Vaccines & Immunotherapeutics

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“…C. difficile strains R20291 (Stabler et al, 2009), CD646 (Keel et al, 2007), JIR8094 (O'Connor et al, 2006) and the gluD mutants (Table 1) were grown anaerobically (10 % H 2 , 10 % CO 2 and 80 % N 2 ) in TY (tryptose yeast extract) broth or TY agar as described previously (Dupuy & Sonenshein, 1998). Escherichia coli strain S17-1 (Teng et al, 1998) used for conjugation was cultured aerobically in LB and supplemented with chloramphenicol (30 mg ml 21 ) or ampicillin (100 mg ml 21 ), when needed.…”

Section: Methodsmentioning

confidence: 99%

Clostridium difficile glutamate dehydrogenase is a secreted enzyme that confers resistance to H2O2

2014

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Clostridium difficile produces an NAD-specific glutamate dehydrogenase (GDH), which converts L-glutamate into a-ketoglutarate through an irreversible reaction. The enzyme GDH is detected in the stool samples of patients with C. difficile-associated disease and serves as one of the diagnostic tools to detect C. difficile infection (CDI). We demonstrate here that supernatant fluids of C. difficile cultures contain GDH. To understand the role of GDH in the physiology of C. difficile, an isogenic insertional mutant of gluD was created in strain JIR8094. The mutant failed to produce and secrete GDH as shown by Western blot analysis. Various phenotypic assays were performed to understand the importance of GDH in C. difficile physiology. In TY (tryptose yeast extract) medium, the gluD mutant grew slower than the parent strain. Complementation of the gluD mutant with the functional gluD gene reversed the growth defect in TY medium. The presence of extracellular GDH may have a functional role in the pathogenesis of CDI. In support of this assumption we found higher sensitivity to H 2 O 2 in the gluD mutant as compared to the parent strain. Complementation of the gluD mutant with the functional gluD gene reversed the H 2 O 2 sensitivity.

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Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium

Cited by 425 publications

References 69 publications

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology

A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity againstClostridium difficileinfection in mice and hamsters

Clostridium difficile glutamate dehydrogenase is a secreted enzyme that confers resistance to H2O2

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