Colonization resistance is defined as the mechanism by which bacterial strains belonging to the normal flora in the intestine are capable of preventing implantation (ie they form a barrier) of pathogenic bacteria. The project studies: the barrier mechanism; the mechanism by which Clostridium difficile overcomes the barrier effect; the antibiotic substance produced by the barrier microflora. C. difficile is often a hospital-acquired organism and the result. Two of the project participants have developed simplified models in mice that represent resident microflora (ie C. indolis, C. cocleatum and C. fusiformis (model 1), which are active against C. difficile implantation. In the second model the reference strain Ruminococcus gnavus secretes an antibiotic substance active towards C. perfringens and other bacteria. Results to date show that the barrier strains to C. difficile can associate with the gut mucous layer, and can degrade it, and this may result in the production of numerous metabolites which may also play a role in the barrier effect, thereby affecting human health. C. difficile can overcome the barrier effect and colonize the intestine under certain circumstances. Several potential colonization factors are adhesins, flagella and surface layer proteins and proteases. Bacterial proteins implicated in adhesion or colonization are generally immunogenic and so the final goal is vaccine (which will produce antibodies) development against this gut pathogen. The biochemical characterization of the bacteriocin effective against C. perfringens has been achieved and its sequence determined. This substance could have therapeutic applications.
