|Biology of Gram-positive Pathogens - CNRS URA 2172|
|HEAD||Dr TRIEU-CUOT Patrick / firstname.lastname@example.org|
|MEMBERS||CALIOT Marie-Elise / COLLINS Michael / Dr DEBARBOUILLE Michel / Dr DRAMSI Shaynoor
Dr DUBRAC Sarah / GUERIRI Ibtissem / KONTO GHIORGHI Ioan / Dr MISTOU Michel-Yves
Dr MORIKAWA Kazuya / Dr MSADEK Tarek / POUPEL Olivier / Pr POYART Claire
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 (GBS) 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
Our aim was to identify inflammatory molecules that are released by GBS and that interact with the Toll-like receptor (TLR) 2. We demonstrated that mature lipoproteins are the major TLR2-activating factors released by GBS and that they significantly contribute to GBS sepsis.
We also showed that S. agalactiae NEM316 expresses two class C sortases (SrtC3-C4) and three LPXTG proteins (Gbs1474, Gbs1477, and Gbs1478) that polymerize to form pili. Gbs1477 constitutes the major component of the pilus whereas Gbs1474, a minor associated component, likely anchors the pilus to the cell wall, and Gbs1478 is thought to be the adhesin.
S. agalactiae, like all streptococcal pathogens, was considered as an aerotolerant but nonrespiring bacterium. However, we demonstrated that it 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 bacterial dissemination by promoting GBS survival in blood.
Gene regulation and stress response
The WalKR two-component system is highly conserved in low G+C Gram-positive bacteria and essential for cell viability. We showed that the WalR regulon in S. aureus includes 9 genes potentially involved in cell wall degradation. Since WalKR is necessary to maintain a normal rate of cell wall biosynthesis and turnover, this regulation could be the key for understanding its essentiality. Among the WalKR regulated genes, 3 appear to be involved in interactions with the extracellular host matrix, opening new perspectives concerning its role in S. aureus virulence.
In Listeria monocytogenes, the degU gene appears to encode an orphan response regulator since the cognate degS histidine kinase gene is absent. DegU is required for expression of several motility and chemotaxis genes, including the flaA and motAB genes, for biofilm formation, and for virulence. We have inactivated the phosphorylation site of DegU in vivo and shown that although the protein retains much of its activity, acetyl phosphate levels in the cell likely influence its activity.
Keywords: Gram-positive bacteria, surface proteins, virulence factors, stress response, signal transduction
Dubrac, S., and T. Msadek. 2004. Identification of genes controlled by the essential YycG/YycF two-component system of Staphylococcus aureus. J Bacteriol 186:1175-1181.
Lalioui, L., E. Pellegrini, S. Dramsi, M. Baptista, N. Bourgeois, F. Doucet-Populaire, C. Rusniok, M. Zouine, P. Glaser, F. Kunst, C. Poyart, and P. Trieu-Cuot. 2005. The SrtA sortase of Streptococcus agalactiae is required for cell wall anchoring of proteins containing the LPXTG motif, for adhesion to epithelial cells, and for colonization of the mouse intestine. Infect Immun 73:3342-3350.
Dramsi, S., E. Caliot, I. Bonne, S. Guadagnini, M. C. Prevost, M. Kojadinovic, L. Lalioui, C. Poyart, and P. Trieu-Cuot. 2006. Assembly and role of pili in group B streptococci. Mol Microbiol 60:1401-1413.
Yamamoto, Y., V. Pargade, G. Lamberet, P. Gaudu, F. Thomas, J. Texereau, A. Gruss, P. Trieu-Cuot, and C. Poyart. 2006. The Group B Streptococcus NADH oxidase Nox-2 is involved in fatty acid biosynthesis during aerobic growth and contributes to virulence. Mol Microbiol 62:772-785.
Dubrac, S., I. Gomperts Boneca, O. Poupel, and T. Msadek. New insights into the WalK/WalR (YycG/YycF) essential signal transduction pathway reveal a major role in controlling cell wall metabolism and biofilm formation in Staphylococcus aureus. 2007. J Bacteriol 189:8257-8269
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Activity Reports 2007 - Institut Pasteur
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