Biology of Gram-positive Pathogens - CNRS URA2172  

  MEMBERSCALIOT Marie-Elise / COLLINS Michael / Dr DEBARBOUILLE Michel / Dr DRAMSI Shaynoor
Dr MISTOU Michel-Yves / Dr MORIKAWA Kazuya / Dr MSADEK Tarek / Prof. POYART Claire

  Annual Report

The main goals of our research activity aim at elucidating new pathways/mechanisms involved in the pathogenesis of low GC% Gram-positive pathogens, using Staphylocccus aureus and Streptococcus agalactiae as models for extracellular pathogens and Listeria monocytogenes as a model intracellular pathogen. Our main research topics include bacterial surface components involved in interactions with the host, metabolic adaptation and virulence, and virulence gene regulation in relation to stress response and environmental adaptation.

Bacterial surface components involved in virulence

An in silico genome analysis indicated that S. agalactiae strain NEM316 encodes four class C sortases. We demonstrated that NEM316 expresses only the srtC3-C4 locus which encodes three surface proteins (Gbs1474, Gbs1477, and Gbs1478) that polymerize to form appendages resembling pili. Analysis of this locus revealed that Gbs1477 and either SrtC3 or SrtC4 are required for pilus biogenesis. This study opens new perspectives for studying structures involved in bacteria-host interactions in pathogenic streptococci.

Metabolic adaptation and virulence

S. agalactiae, like all streptococcal pathogens, was considered as an aero tolerant but non respiring bacterium. However, we demonstrated that GBS was able to undergo respiration metabolism if supplied with two essential respiratory components found in the host, menaquinone (vitamin K) and heme, using cytochrome bd quinol oxidase as the terminal oxidoreductase. Respiration-defective strains were attenuated for virulence in a neonatal rat sepsis model, suggesting that respiration metabolism facilitates GBS dissemination by promoting its survival in blood.

Gene regulation and stress response

The YycG/YycF two-component system is very highly conserved and appears to be specific to low G+C Gram-positive bacteria. This system is required for cell viability, although the basis for this and the nature of the YycF regulon remained elusive. We have defined the YycF recognition sequence allowing us to identify members of the YycF regulon in S. aureus, including the ssaA, isaA and lytM genes, and shown that the system is essential for cell viability. We have also shown that there is a direct relationship between the amount of YycF in the cell and the ability to form biofilms.

In Listeria monocytogenes, the degU gene appears to encode an orphan response regulator since the cognate degS histidine kinase gene is absent. A significant decrease in the LD50 of the degU mutant strain compared to that of the otherwise isogenic parental EGDe, was observed in a murine model of infection. DegU is required for expression of several motility and chemotaxis genes, including the flaA and motAB genes and for the formation of efficient biofilms by L. monocytogenes. We have inactivated the phosphorylation site of DegU in vivo and shown that the protein retains much of its activity, indicating that the unphosphorylated form is active.

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Publications 2006 of the unit on Pasteur's references database

Activity Reports 2006 - Institut Pasteur
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