Integrative Biology of Emerging Infectious Diseases (IBEID) / Principal investigators
Biology of Gram-positive Pathogens Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
Research area of the Unit
The main goals of our research activity reflect our common interests and complementary approaches aimed at elucidating new pathways/mechanisms involved in the pathogenesis of low GC% Gram-positive bacteria, using S. aureus, S. agalactiae, and S. gallolyticus, as models of extracellular human pathogens.. Our research topics include the study of bacterial surface components involved in interactions with the host, of relationships between metabolic adaptation and virulence, and gene regulation in relation to host environment and adaptation to stress responses.
Our main research topics are:
• Gene regulation in relation with :
- Expression of virulence
- Host-pathogen interaction
- Antibiotic resistance
• Bacterial surface components and interaction with the host :
- Lipoteichoic acids
- Cell-wall anchored proteins
Contribution to the programme
Role of streptococcal surface-anchored proteins in virulence
S. agalactiae is a major pathogen of human neonates and an emerging pathogen in adults. Our aim is to characterize the surface-anchored proteins that bind to epithelial, endothelial, primary cells, and or extracellular matrix components and to explore their role in pathogenesis using mammalian animal models. Our project also aims at deciphering the role of the pili of Streptococcus gallolyticus, an emerging pathogen causing endocarditis and associated to colon cancer, in host colonization and to identify the signaling pathways induced in human colonic epithelial cells.
Cell wall signaling and host-S. aureus interactions
S. aureus is a major human pathogen that can alternate between commensal and pathogenic lifestyles. We are characterizing cell envelope signaling pathways and their impact on host-pathogen interactions, virulence and antibiotic resistance. We use murine models to follow inflammatory response, sepsis, and in vivo expression of bacterial virulence genes and we aim at understanding the molecular mechanisms involved in the pathogenic switch and host-pathogen interactions.
References over the past 5 years
1. Konto-Ghiorghi Y, Mairey E, Mallet A, Dumenil G, Caliot E, Trieu-Cuot P. and Dramsi S (2009) Dual role for pilus in adherence to epithelial cells and biofilm formation in Streptococcus agalactiae. PLoS Pathog 5, e1000422.
2. Brinster S, Lamberet G, Staels B, Trieu-Cuot P, Gruss A, and Poyart C. 2009. Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens. Nature 458:83-86.
3. Tazi A, Disson O, Bellais S, Bouaboud A, Dmytruk N, Dramsi S, Mistou M-Y, Khun H, Mechler C, Tardieux I, Trieu-Cuot P, Lecuit M, Poyart C (2010) The surface protein HvgA mediates Group B streptococcus hypervirulence and meningeal tropism in neonates. J Exp Med 207: 2313-2322.
4. Hiron A, Falord M, Valle J, Debarbouille M, and Msadek T (2011) Bacitracin and nisin resistance in Staphylococcus aureus: a novel pathway involving the BraS/BraR two-component system (SA2417/SA2418) and both the BraD/BraE and VraD/VraE ABC transporters. Mol Microbiol 81: 602-622.
5. Pichon C, du Merle L, Caliot E, Trieu-Cuot P, and Le Bouguénec, C (2012) An in silico model for identification of small RNAs in whole bacterial genomes : Characterization of antisense RNAs in pathogenic Escherichia coli and Streptococcus agalactiae strains. Nucl Acids Res 40:2846-2861 (Epub 2011 Dec 1).
6. Falord M, Karimova G, Hiron A, and Msadek, T (2012). GraXSR proteins interact with the VraFG ABC transporter to form a five-component system required for cationic antimicrobial peptide sensing and resistance in Staphylococcus aureus. Antimicrob Agents Chemother 56:1047-1058.
7. Caliot E, Dramsi S, Chapot-Chartier M-P, Courtin P, Kulakauskas S, Péchoux C, Trieu-Cuot P, and Mistou M-Y (2012) Role of the group B antigen of Streptococcus agalactiae: a peptidoglycan-anchored polysaccharide involved in cell wall biogenesis. PloS Pathog (In press).