In the field of host-pathogen interaction and disease modelling, it is now widely assumed that infection outcome is the combined result of many factors including the virulence potential of microorganisms, the manipulation of signaling pathways and the immuno-metabolic host responses. In addition, evolutionary and ecological factors are involved in the outcome of infections. Therefore, we are engaged in an integrative approach that brings together clinical observations, fundamental and clinical microbiology, molecular biology, immunology, cell biology, and structural biology to identify the bacterial determinants influencing the outcome of infections and to determine markers for diagnosis, as well as new targets for prevention and treatment.

To this end, we focus on model organisms that are bacterial inhabitants of the mucosa and the skin, Neisseria meningitidis and Staphylococcus aureus. The strength of these models lies in their ability to colonize a significant proportion of the human population, with over 20% of individuals carrying N. meningitidis or S. aureus, and the extreme severity of the diseases they may cause. We address two main questions: 

• How do bacteria take advantage of host responses to cause disease? 
• How does bacterial adaptation to the host influence virulence?

Therefore, two main research axes are being pursued.

• The first approach focuses on the mechanisms and consequences of the interaction of extra-cellular bacterial pathogens with endothelial cells using Neisseria meningitidis as paradigm. This pathogen following bloodstream invasion from the nasopharynx establishes a strong interaction with the capillaries. This interaction is associated with the occurrence of meningitis and Purpura fulminans. Our objectives are to provide a coherent picture of meningococcal pathogenesis by dissecting the interaction between meningococci and endothelial cells at the molecular, cellular, and tissular levels.
   
• The second approach aims to provide new insights into the pathogenesis of Staphylococcus aureus, which is one of the deadliest bacteria in Western countries. We are particularly committed to the study of virulence factors associated with chronic infections, and have launched translational research projects involving cohorts of children with chronic S. aureus infections (including cystic fibrosis and genetic dermatoses). Bacterial adaptation explains why bacteria persist in infected sites despite immune response and antibiotic treatment. Our two main objectives are: i) to identify the genetic mutations modulating bacterial toxicity and inflammation, through unbiased proteogenomic analysis of host-adapted S. aureus clinical isolates, and ii) to study the impact of S. aureus adaptation in vitro and in vivo, focusing on the host immune response and disease outcome.