Salmonella are enteric bacteria which cause severe infections in man and animals. Our research is aimed at defining adapted and new strategies to prevent salmonellosis. For this purpose, studies are focused on (i) the regulatory systems governing Salmonella entry into epithelial cells; and (ii) the mechanisms by which Salmonella survive in the environment, including their hosts.
Prevention of Salmonella infections (Michel Y. Popoff)
The crucial step in the pathogenesis of Salmonella is their ability to penetrate ileal epithelial cells. Most of the genes involved in this infectious process are clustered at centisome 63 of the Salmonella chromosome, which has been referred to as Salmonella pathogenicity island 1 (SPI 1). These genes encode components of a type III secretion system and bacterial virulence factors that are translocated by the secretion system into the cytosol of epithelial cells. The ability of Salmonella to enter into host cells is subject to very complex regulation. The regulatory mechanisms involve SPI 1-encoded regulatory proteins as well as established global regulation pathways. By using transcriptional fusions with SPI 1 genes, we identified two families of compounds (fatty acids and aromatic acids) preventing in vitro expression of invasion genes, although growth conditions were optimal for their expression. These compounds are devoid of bactericidal or bacteriostatic activity on Salmonella. The sodium caprylate, a short-chain fatty acid recognized as safe substance for humans and used as food additive, drastically reduces the number of bacteria in spleen of C57Bl/6 mice orally infected subsequently by S. typhimurium, S. enteridis or S. dublin. In addition, this compound protects C57Bl/6 mice against subsequent challenge with 25 LD50 of S. typhimurium. Used as chemical additive in foods or drinking water, this product might reduce the incidence of salmonellosis in animals, thereby reducing further human contaminations. It appears as a promising alternative to the widespread use of antibiotics in foods for animals. Use of Na-caprylate to prevent salmonellosis has been patented by the Institut Pasteur. Mechanisms by which Na-caprylate prevents expression of invasion genes in Salmonella are under studies.
Functional analysis of the RpoS regulon in Enterobacteriaceae : role in general stress resistance, starvation survival, and virulence of Salmonella (Françoise Norel)
The alternative sigma factor RpoS plays a central role in stationary phase survival and adaptation of Enterobacteriaceae to stress conditions. Most work on the RpoS regulon has been in Escherichia coli K-12 and more than 50 genes regulated by RpoS have been identified so far. Interestingly, RpoS is essential for virulence and persistance in mice of the closely related enteric pathogen Salmonella. To perform a functional analysis of the RpoS regulon in Salmonella, we isolated RpoS-activated lacZ gene fusions from a bank of S. typhimurium mutants. Two thirds of the fusions mapped in orthologs of genes in E. coli K-12, most of which are ORFs of unidentified function. These ORFs might contribue to adaptation of Enterobacteriaceae to growth conditions in natural environments. One-third of the fusions mapped to Salmonella DNA regions not present in E. coli K-12. Further characterization of two of these led to the identification of katN, a gene encoding a non-haem catalase not previously described in Salmonella. katN is not widespread in Enterobacteriaceae but orthologs of katN are found in enterohemorrhagic E. coli O157, Klebsiella pneumoniae and Pseudomonas aeruginosa.
The WHO collaborating centre for reference and research on Salmonella (Michel Y. Popoff)
The WHO collaborating centre for Salmonella is located in the unit. This WHO Collaborating Centre only studies strains sent by the National Reference Centre for Salmonella. This year, the centre has characterized 92 strains, described 26 new serotypes and 1 new antigenic factor, and sent 238 reference strains to National reference centres for Salmonella..