Staphylococcus aureus is ne of the most frequently reported antibiotic-resistant bacteria; this opportunistic pathogen belongs to the ESKAPE group, an acronym given to six pathogens responsible for nosocomial infections that that pose a threat to health worldwide. Despite recent reports of efficient prophylactic measures, S. aureus remains a leading cause of community- and healthcare-associated diseases ranging from minor skin infection to fatal bacteremia. Its “success” as a pathogen is due to the expression of numerous virulence factors, a high adaptability to many biotopes, and to the emergence of multidrug-resistant strains. Our experimental approaches are mainly bacterial genetics, genomics and physiology.