Pathogenesis of Anaerobic Bacteria Laboratory
Anaerobic bacteria are part of the normal human endogenous flora . The quantity of anaerobic bacteria increases progressively in the intestinal tract down to the colon, where they are a thousand fold more numerous than the aerobic bacteria. Some of these anaerobic bacteria are part of the infectious processes, often on the basis of an opportunistic event or following anatomo-physiological perturbations of infectious sites. The anaerobic bacterium pathogenicity lies in the bacteria themselves but can be increased due to host-dependent factors (immunodeficiency) as well as by the bacterial environment. Bacteroides and Clostridium are the two major anaerobic bacteria to be found in the colic flora.
Among the pathogen Clostridia, Clostridium difficile is responsible for 15 to 25% of all cases of antibiotic-associated diarrhoea and for the majority of the pseudomembranous colitis. It is the main enteropathogen bacterium isolated in nosocomial diarrhoea of adults. Since 2003, highly pathogen strains have emerged and the rate and the severity of C difficile infections have dramatically increased. Many virulence factors seem to be involved during the process of C difficile infection; however, the production of two toxins (TcdA and TcdB) plays a major role in the pathogenicity of this bacterium.
The main research activities of the laboratory are focused on the mechanisms involved in the transcription initiation of the C difficile toxin encoding genes, in the regulation of their expression both during growth phases (transition phase) and in response to various environmental signals (carbon sources, sulfur amino acids). Toxin secretion is also studied. We are also identifying factors involved in the colonisation of the intestinal tract by C difficile (sporulation, adhesion, adaptation, multiplication) using an in vitro and in vivo comparative analysis of genes expressed of C. difficile when recovered from infectious context (axenic mouse model). We are currently conducting a genomic and transcriptomic comparative analysis of highly pathogen strains. We expect to identify factors responsible for the emergence and the hypervirulence of epidemic strains both in the USA and in Europe.