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Characterization of the human pathogen Clostridium difficile and the interplay with the host microbiome

Clostridium difficile is the leading cause of antibiotic-associated diarrhoea worldwide. Currently there are only three antibiotic therapies to treat CDI—vancomycin, metronidazole, and fidaxomycin and no licenced vaccine. The efficacy of these antibiotics varies, and a high proportion of patients relapse with CDI. The pathogenies of C. difficile is a complex network of interactions between a number of different virulence factors linked to survival in the host, such as production of toxins, biofilm formation, and modulation of the host microbiota. We have traced the transcontinental spread of C. difficile and attributed genetic variation in antibiotic resistance as one of the key factors in increased CDI spread. Moreover, we have identified a compound, para-cresol, produced almost exclusively by C. difficile, which inhibits the growth of other healthy intestinal bacteria, thus promoting colonization and relapse of C. difficile infection. We have harnessed transcriptomics, genomics and metabolomics to investigate the role of antibiotic-associated dysbiosis of the intestinal microbiota on C. difficile colonization, disease, and relapse.

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