BaPS

Clostridium difficile is responsible for a large proportion of post-antibiotic diarrhoea and most pseudomembranous colitis in humans and of many intestinal infections in livestock. The first step of C. difficile infection (CDI) corresponds to the colonization of the host. This step is made possible by a dysbiosis of the microbiota, following most of the time antibiotic exposure. The resulting disruption of the barrier effect favors germination of the infectious spores and implantation of C. difficile in its intestinal niche. Clinical signs arise from the effect of the toxins (main virulence factors) on intestinal cells and tissues. Infection outcome is known to be related to the strain virulence but also to the intensity of the host response, both innate and adaptive. Indeed, inflammatory response, essential for the pathogen clearance, may also exert deleterious effect for the host if uncontrolled. CDI is treated by antibiotics but recurrent infections occur frequently, leading in some patients to multiple recurrences experiences, that are relapses for most of the time. The persistence of the initial strain in the patient, in an asymptomatic colonization status, has been long time related to spore production, but recently the hypothesis of persistence of C. difficile within a biofilm was also proposed.

With more than 20 years of research into C. difficile, our team is recognized to have a great expertise on C. difficile pathophysiology and CDI. Our objectives are both to go on increasing basic knowledge on the interactions between C. difficile and the host and to identify new strategies to fight against CDI. Several projects have been developed to address these questions: the mechanisms underlying the increase of infectious risk following dysbiosis of the intestinal microbiota; the study of C. difficile biofilm formation and architecture to understand interactions with the digestive mucosa; the characterization of several important polymeric components of the bacterial surface (e.g. flagella, polysaccharides, peptidoglycan) as new targets for C. difficile inhibition; the study of the innate (and its regulation) and adaptive host response to virulence factors; development of therapeutic innovations such as mucosal vaccines or probiotics. These projects are grouped into 4 thematic axes (see below).

To carry out these projects, the unit currently comprises, as permanent staff, 12 teachers-researchers, 2 technicians (research and teaching) and a secretary. A third technician (research and teaching) and one laboratory aid are present as fixed-term paid contract funded by the pharmaceutical Faculty. We are currently supervising 3 PhD, 3 M2 students, 3 research engineers and one assistant engineer under own resources (external contracts). We have a variety of tools and expertises, in anaerobic bacteria, molecular bacteriology and genetic manipulation of Clostridia, cellular microbiology, medical microbiology, and rodent CDI models.