Research Groups

[1030] Staphylococcus aureus: antibiotique résistance et signalisation

Our laboratory studies the mechanisms of antibiotic resistance and environmental sensing systems primarily in the human pathogen, Staphylococcus aureus. Recently, we have also begun related work on antibiotic resistance with Enterococcus faecium, Listeria monocytogenes, and Streptococcus pneumonia.


Our research and our interests focus on:

                The molecular details of antibiotic resistance

                The development of techniques to restore MRSA strain sensitivity to b-lactam antibiotics

                Understanding of signalling systems that detect and respond to cell wall damage

                The analysis of the biosynthesis and folding of penicillin binding proteins

                Understanding the essential S. aureus redox sensor Spx and its regulon


The last two steps of peptidoglycan biosynthesis take place outside the plasma membrane and are accomplished by enzymes called penicillin binding proteins. Beta-lactam antibiotics and the glycopeptide class (for example, teicoplanin and vancomycin) target these enzymes or their substrates and thereby block peptidoglycan polymerization and crosslinking.  The resistance to all types of beta-lactams shown by MRSA (methicillin resistant S. aureus) strains with the exception of the last generation cephalosporins (p.ex ceftaroline) occurs by the horizontal acquision of the SCCmec element, which encodes a variant penicillin binding protein (PBP2A). The acquisition and expression of PBP2A is the fundamental event underlying the global public health problem associated with MRSA.


Our work seeks to understand how antibiotic resistance appears, develop strategies to restore sensitivity to antibiotics, and to discover new avenues for future therapeutic development. We have recently discovered, for example, that PBP2A requires at least two dedicated extracellular protein chaperones to assure its proper folding and quality control. Proper folding is especially critical since PBP2A is allosterically regulated-- a feature that explains its broad resistance to so many beta-lactam antibiotics. We have expanded our research effort to examine all aspects of PBP2A (and related PBPs) enzymatic properties and protein folding using genetic, biochemical and biophysical techniques.


Other than antibiotics and cellular redox equilibrium, we have had a longstanding interest in the transcriptional regulation of toxins such as toxic shock superantigen (TSST-1) of S. aureus. Under both aerobic and anaerobic conditions, we have identified multiple transcription factors that control the expression of the toxin. Most of these factors exert negative regulation and have helped us define molecular explanations for environmental triggers of toxin production as well as understanding how sporadic random mutation could impact toxin gene expression.