|Toxins and Bacterial Pathogenesis - CNRS URA2172|
|HEAD||Prof. MOCK Michèle / email@example.com|
|MEMBERS||COUTURE-TOSI Evelyne / DAVISON Sophie / Dr FOUET Agnès / Dr GLOMSKI Ian
Dr GOOSSENS Pierre / Prof. KOLSTO Anne-Brit / Dr MARY-POSSOT Odile / Dr MELONI Mauro
MOYA-NILGES Marie / Dr RANCK Jean-Luc / Dr SYLVESTRE Patricia
Dr VAN SCHAIK Willem
Bacillus anthracis, the aetiological agent of anthrax, is a Gram-positive, spore-forming, extra cellular bacterium. The spore is both the form of persistence in the environment and the infectant form. Two toxins, and a poly-glutamic acid, antiphagocytic, capsule are the main virulence factors
The exosporium is the most external structure of the spore. It consists of a paracrystalline basal layer and of BclA, a collagen-like glycoprotein. Other spore components required for the assembly of the paracrystalline layer have been identified.
Metabolic pathways and biodiversity
Among the main groups defined worldwide for B. anthracis strains, those of the sub-group B2, mostly found in France, exhibit specific sugar utilization. A1 strains use starch but not gluconate, and conversely for B2 strains. A comparative genomic analysis has revealed mutations affecting enzyme activities potentially involved in sugar utilization.
Vegetative form surface
Four proteins are necessary for capsule synthesis. A fifth protein catalyzes the capsule covalent anchoring to the peptidoglycan.
“Sortases” catalyze the covalent anchoring of proteins harboring an “LPXTG” motif. B. anthracis possesses three sortases and 14 “LPXTG” proteins. We have constructed mutants of each of the sortases. We have characterized an “LPXTG” protein that is anchored by sortase A. We are defining B. anthracis sortase repertoires.
Regulation of virulence factors synthesis
Toxin components are maximally synthesized at the end of the exponential phase. Transition state regulators, including CodY, repress gene expression during exponential phase. CodY implication in toxin, capsule and AtxA, a B. anthracis master regulator, gene expression is under study. B. anthracis stringent response has been characterized. There is a single rel gene in B. anthracis.
In vivo analysis of bioluminescent B. anthracis dissemination in mice in real time (Figure) has shown unidentified portals of entry. Characterization of the dynamics of germination, multiplication and dissemination will give clues to innate control mechanisms and how B. anthracis may escape.
Innate and adaptive immunity
We have shown that group IIA phospholipase A2, secreted by inflammatory cells, is highly anthracidal in vitro and in vivo. Cell transduction pathways involved in early recognition of spores are analyzed.
A non-living anthrax vaccine composed of protective antigen and inactivated spores has been devised for human use. We have shown that the protective immunity afforded by spore immunization is dependent on cellular immunity involving CD4 T lymphocytes and gamma interferon.
|Publications 2006 of the unit on Pasteur's references database|
Activity Reports 2006 - Institut Pasteur
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