|Pathogenesis of Mucosal Bacteria|
|HEAD||Prof. LABIGNE Agnès / firstname.lastname@example.org|
|MEMBERS||Dr BARRIERE Anne-Charlotte / BONIS Mathilde / Dr BUSSIERE Françoise/ Dr DE REUSE Hilde
Dr EL GHACHI Meriem / Dr GOMPERTS BONECA Ivo / Dr LE BOUGUENEC Chantal
MARTINEZ-JEHANNE Vanessa / MATHIEU Aurélie / Dr PICHON Christophe
ROURE Sophie / SCHAUER Kristine / THIBERGE Jean-Michel / THIBONNIER Marie / Dr TOUATI Eliette
The research work of the Unit is focused on the study of human mucosa-associated bacterial pathogens: a) Helicobacter pylori, associated with the inflammatory gastroduodenal diseases (chronic gastritis, peptic ulcer, lymphoma and gastric cancer), and b) pathogenic Escherichia coli.
a) Helicobacter pylori
Adaptation of H. pylori to the gastric environment presents specific features including an essential K+ channel. Regulation of this response is mediated by NikR, Fur and ArsR transcriptional regulators. The tridimensional structure of the nickel-responsive regulator NikR of H. pylori was solved, and a novel mechanism energized by the TonB/ExbB/ExbD machinery to transport nickel across the bacterial outer membrane was described.
H. pylori peptidoglycan hydrolases (AmiA, Slt, and MltD) involved in PG assembly were shown to play a major role in cell growth, morphology (bacillary/ coccoid) as well as in the innate immune response. Deficient mutants in any of the 3 hydrolases were impaired in their ability to colonize the mouse gastric mucosa, suggesting that they might be considered as new putative therapeutic targets to eradicate H. pylori.
Host response associated with H. pylori infection was investigated in mice using the Affymetrix® DNA microarrays. genes involved in immune response, transcription regulation, signaling cascade, showed a modified expression. Effects of host DNA repair genes were also investigated.
Genetic, biochemical and structural analyses of functions associated with DNA repair lesions, recombination mechanisms and replication control in H. pylori were conducted to characterize biological systems in H. pylori that are distinct from those commonly found in the other bacteria and to study their specificity and their impact on H. pylori biology (MutS2 and HobA studies).
Comparative genomics of clinical isolates of H. pylori associated with distinct pathologies allowed us to delineate clusters of isolates, one of which containing exclusively MALT lymphoma associated isolates. The genome of strain B38, a representative of this cluster, was sequenced and is currently analyzed to identify unique characteristics of those MALT lymphoma isolates.
b) Pathogenic Escherichia coli
Role of bacterial metabolic factors in host colonization. Preliminary studies suggest that most E. coli isolates causing renal infections are able to use, as carbon sources, sugars that are not metabolized by strains of the intestinal tract. Using allelic exchange, several pathways of interest were knocked out to compare in vitro and in vivo the relative fitness of the mutants and of the parental strains by means of competition assays, growth in urine, biofilm formation, as well as colonization of the intestine and the urinary tract of mice.
Interaction of uropathogenic E. coli with kidney cells. We characterized the interaction of uropathogenic E. coli strains with collecting duct cells, and showed for the first time that bacteria could invade kidney cells.
|Publications 2006 of the unit on Pasteur's references database|
Activity Reports 2006 - Institut Pasteur
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