|Director : Popoff Michel Yvan (email@example.com)|
Salmonella are bacteria which cause severe infection in man and animals. The crucial step in the infection is the entry of bacteria into ileal epithelial cells. This phenotype is governed by a set of genes, expression of which is controlled by regulatory systems in response to environmental conditions. Research is centered on the characterization of these regulatory systems in order to prevent salmonellosis. The role of the RpoS regulon, the set of genes whose expression is controlled by the sigma factor RpoS, in the virulence of Salmonella and in the adaptation of these bacteria to stress conditions is also studied. These studies are aimed at identifying the mechanisms by which Salmonella survive in the environment, including their hosts, to define adapted strategies for prevention.
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). Their expression is tightly regulated in response to environmental conditions. By using transcriptional fusions with SPI-1 genes, we identified chemical compounds preventing in vitro expression of invasion genes, although growth conditions were optimal for their expression. Furthermore, sodium caprylate, a fatty acid recognized as safe substance for humans and used as food additive, drastically reduced the number of bacteria in spleen of C57Bl/6 mice orally infected subsequently by S. typhimurium, S. enteridis or S. dublin. Activity of caprylate derivatives was further examined. It appeared that 2-hydroxy and 8-hydroxy caprylate, but not 2-amino and 8-amino caprylate, prevented also expression of transcriptional fusions. S. typhi mutants, in which invasion genes expression is no longer repressed by caprylate, were isolated and are under studies. Used as chemical additive in foods or drinking water, sodium caprylate might reduce the incidence of salmonellosis in animals, thereby reducing further human contaminations. This compound appears as a promising alternative to the widespread use of antibiotics in foods for animals.
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. One-third of the fusions mapped to Salmonella DNA regions not present in E. coli K-12. This suggests that the composition of the RpoS regulon differs markedly in the two species. Most of the fusions mapped in genes of unidentified function. One of these, the katN gene, was shown to encode a non-haem catalase. katN is not present in E. coli K-12 but is conserved in enterohemorrhagic E. coli O157, Klebsiella pneumoniae and Pseudomonas aeruginosa, For most of them, the remaining genes are likely to have metabolic functions. They might contribue to adaptation of Enterobacteriaceae to growth conditions in natural environments.
The WHO Collaborating Centre for Reference and Research on Salmonella (Michel Y. Popoff)
The objective of this WHO Collaborating Centre is the characterization of new Salmonella serovars and new antigenic factors associated with the somatic or flagellar antigens. The centre studies only strains sent by National Reference Centres for Salmonella. This year, the centre described 12 new serovars and sent 383 reference strains to National Reference Centres for Salmonella. It has also published the new editions of the "Antigenic formulas of the Salmonella serovars" and the "Guidelines for the preparation of Salmonella antisera".
|Publications of the unit on Pasteur's references database|
|Office staff||Researchers||Scientific trainees||Other personnel|
Ondet Maxence (firstname.lastname@example.org)
Norel Françoise, IP (chargé de recherche; email@example.com)
Popoff Michel Y., IP (professor; firstname.lastname@example.org)
Ferry Rachel, student
Tedin Karsten, post-doc
Fayolle Corine (Technicienne qualifiée; email@example.com)
Guibourdenche Martine (Ingénieur; firstname.lastname@example.org)
Hermant Daniel (Technicien supérieur; email@example.com)
Robbe-Saule Véronique (Technicienne supérieure; firstname.lastname@example.org)