INTRODUCTION

Staphylococci are a genus of bacteria remarkably adept at causing a variety of human and animal diseases. These range from relatively benign skin infections, such as impetigo, to much more serious ones, including endocarditis, osteomyelitis, toxic shock syndrome, and those associated with implanted medical devices. In fact, the staphylococci are a leading cause of nosocomial infections worldwide, and the continuing emergence of highly drug-resistant strains has created an immediate need for the development of new antimicrobial therapies and strategies. Since the identification of the accessory gene regulator (Agr) quorum sensing system in Staphylococcus aureus, and subsequently in other staphylococcal species, it has been assigned a central role in the regulation of staphylococcal virulence. As such, it has attracted substantial attention as a potential target for controlling staphylococcal disease.

Although recent studies have shown that virulence-gene regulation by Agr is considerably more complex in vivo than initially understood from studies in vitro, it remains clear that expression of Agr, or even lack thereof, is an important determinant in staphylococcal disease development. agr mutants have been shown to be attenuated for virulence in some animal models of infection, including a murine arthritis model, an osteomyelitis model, and a skin abscess model (reviewed in (34)). It has also been shown that expression of Agr, and of Agr-regulated exotoxins, facilitates escape of S. aureus internalized by epithelial cells (49).