Staphylococcal Pathogenesis: from the bug to host-responses
Staphylococcus aureus (SA) represents a major threat for public health worldwide (30% of nosocomial and community-acquired infections). SA pathogenesis depends on the expression of numerous adhesins and exoproteins that impair the host and cell defenses. Expression of these virulence factors is tightly regulated by a complex network involving transcriptional factors and regulatory RNAs. We aim at getting a global characterization of SA diseases by an integrative approach from bed to bench and reverse to understand the occurrence, mechanisms of diseases and microbial clearance.
Four research axes are intertwined:
1- Characterisation of new and/or emerging staphylococcal diseases, molecular epidemiology and population genetics of staphylococci.
This research benefits from the National Reference Center for Staphylococci (NRCS) network of clinicians and microbiologists, and associated biobanks,
2-Pathophysiology and new therapeutic approaches:
*Pathophysiology of toxin-associated diseases.
– Panton Valentine leukocidin, other pore-forming toxins, phenol soluble modulins; searching for their cell host receptors and deciphering their impact on the innate immune cell response (col T. Henry); looking for genetic predispositions to these disease (col C. Picard); deciphering the mechanisms of antibiotic-mediated modulation of expression of toxins and innate-immmune effector; exploring the synergistic role of influenza and staphylococci in lung infections (col B. Lina);
– Menstrual toxic shock syndrome: searching how vaginal microflora and local immunity controls the ecology of aureus and its virulence (col D Muller, C Pingent-Combaret, J Thioulouse, V Brun); deciphering toxic shock toxin-1 trancytosis across vaginal epithelium and putative synergistic role of other S. aureus toxins (col S. Paul); looking for host predisposition to the diseases (comportment, genetic…)
*Pathogenesis of staphylococcal bone and joint infection:
Deciphering the impact of Staphylococcus spp. on osteoblasts and osteoclasts; understanding the mechanisms involved in internalization and intracellular persistence; characterizing the adhesion and the biofilm formation in the context of prosthetic joint infections; studying the effect of antibiotics and innovative therapies against intraosteoblastic staphylococci and biofilm.
*Pathogenesis of staphylococcal infective endocarditis:
Identification of the bacterial factors involved in the occurrence of Staphylococcus aureus infectious endocarditis in the course of bacteremia: beyond correlation, toward causality. Comparative analysis of whole genomes, transcriptomic and proteomic approaches to identify genotypic or phenotypic bacterial factors essential to the occurrence of endocarditis –and its complications- in the course of bacteremia.
3-Cross-talk in Staphylocococcus-Pseudomonas co-infections
Understanding and deciphering the relationship between S. aureus and P. aeruginosa in co-infection situations. Identify the transcriptional changes induced by the co-existence of both bacteria and the phenotypic impacts. Studying bacterial evolutions during co-infection by genomic and proteomic approaches.
4 – Identification of regulatory RNAs structure-function:
Search for new sRNA, establish their structures (in collaboration with Pascale Romby Lab, IBMC Strasbourg), decipher their function in virulence, metabolism and life-style of S. aureus; identify the co-factors involved in target gene regulation; Expression within host and differential expression according to diseases.
INSERM, university, anr, European FP, FINOVI