The research interests of our group on microbial pathogenesis include the understanding of the early steps of colonization and invasion of the host by Staphylococcus aureus. S. aureus is a major human pathogen which causes a variety of infections, ranging from relatively mild skin and wound infections to life-threatening diseases such as endocarditis and meningitis, and toxin-associated syndromes (e.g., food poisoning and toxic shock syndrome). S. aureus also infects foreign materials, such as prosthetic valves and intravascular catheters, and is also a leading cause of nosocomial bacteremia and community acquired infections. Pathogenicity in this bacteria is based on a wide range of cell wall-associated adhesins (e.g., fibrinogen-, and fibronectin-binding protein) and extracellular toxins (e.g., hemolysins and enterotoxins).
Experiments on S. aureus pathogenesis, have established a correlation between the ability of bacteria to adhere to platelet-fibrin matrices in vitro and genuine bacterial colonization and infectivity in vivo, using the rat model of endocarditis as a readout system. Further in vivo studies were designed to better understand the importance of specific bacterial surface adhesins, including fibrinogen-binding protein, or clumping factor A (ClfA), and fibronectin-binding protein A (FnbA), using isogenic pairs of bacteria producing the ligands or not producing the ligands due to specific inactivation of deletion of their genetic determinants. In short, the results of these experiments showed that inactivation of any surface determinant alone only marginally affected infectivity.
The study of the pathogenic role of individual S. aureus virulence factors, using classical individual gene inactivation of deletion, has yielded inconclusive results likely because the inactivated mutants possessed additional factors that could complement the function of the missing gene in the diseases process. To circumvent this problem, our laboratory has developed an original approach: the transfer of individual virulence determinants from S. aureus into the less pathogenic bacteria Lactococcus lactis and then assess, in the recipient bacteria, the gain of function conferred by the transferred gene both in vitro (adhesion test) and in rats with experimental endocarditis. This approach, called "adoptive pathogenesis", clearly identified clfA, and fnbA genes as critical virulence factors of S. aureus.