Staphylococcus aureus is a major Gram-positive pathogen, responsible for a variety of infections affecting practically every host organ and figuring prominently among the leading causes of sepsis in both nosocomial and community-acquired infections. Treatments have increasingly been thwarted by the rapid acquisition of multiple antibiotic resistance genes, which has contributed to make strains such as methicillin-resistant S. aureus (MRSA) one of the top ten causes of mortality in the United States and a main worldwide health concern.
Research in the «Signaling and Pathogenesis of Staphylococci» group is focused on environmental adaptive responses in Staphylococcus aureus, including the study of bacterial surface components and signal transduction pathways involved in virulence gene expression, host-pathogen interactions, antimicrobial resistance and cell envelope homeostasis. The main goal of our research activity aims at using a multidisciplinary approach to elucidate new pathways involved in pathogenesis of Staphylococcus aureus. Indeed, a detailed understanding of the mechanisms involved in this tenacious bacterium’s considerable capacity for adaptation to the host is essential in developing new therapeutic approaches.
Our group has a long-standing history and well-recognized expertise in Gram-positive molecular genetics of regulatory networks and has been highly implicated in collaborative research projects funded by the European Commission (StaphDynamics, BaSysBio), the ANR (NaBab; GrabIron), the Institut Pasteur (GPH N°9, PTR N° 17, 18, 256 and 336), the Conseil Pasteur-Weizmann and the Vaincre La Mucoviscidose association. Our contributions in Staphylococcus aureus include the discovery of CtsR, a novel thermosensory regulator of stress response; the in-depth characterization of the WalK/WalR two-component system, essential for cell viability and coordinating cell division and cell envelope plasticity, the discovery in S. aureus of several new virulence genes (cymR, stk1) as well as the development of several popular and highly useful genetic tools such as the pMAD plasmid facilitating gene knockouts and chromosomal site-directed mutagenesis. The pMAD plasmid has been distributed to over 300 laboratories around the world and is available to order from the Institut Pasteur Biological Resource Center.
The Signaling and Pathogenesis of Staphylococci Research Group is developing several research topics at the Institut Pasteur:
– bacterial responses to environmental variations and their role in Staphylococcus aureus pathogenesis and interactions with the host;
– the impact of bacterial cell envelope dynamics on host–pathogen interactions, biofilm formation, and the innate immune response;
– antibiotic and antimicrobial peptide resistance mechanisms;
– genome plasticity and the acquisition of new virulence factors.
Recent developments include :
-the discovery and characterization of a novel bacitracin and nisin resistance pathway in S. aureus involving a two-component system and two ABC transporters: BraSR/BraDE/VraDE ;
-the demonstration that the WalKR system controls major staphylococcal virulence genes and is involved in triggering the host inflammatory response ;
-the discovery and demonstration of the ability of S. aureus to develop natural competence for transformation by exogenous DNA, including the acquisition of antibiotic resistance genes.