What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

• A large fraction of bacteraemia cases involve strains lacking functional accessory gene regulator (Agr).
• Agr signalling is restricted to the intracellular environment.
• Staphylococcus aureus can lyse neutrophils from the inside via Agr regulated toxins.
• In some strains, loss of Agr appears to be a trade-off for antibiotic resistance.

Staphylococcus aureus is a major cause of bacteremia, which frequently results in serious secondary infections such as infective endocarditis, osteomyelitis, and septic arthritis. The ability of S. aureus to cause such a wide range of infections has been ascribed to its huge armoury of different virulence factors, many of which are under the control of the quorum-sensing accessory gene regulator (Agr) system. However, a significant fraction of S. aureus bacteremia cases are caused by agr-defective isolates, calling into question the role of Agr in invasive staphylococcal infections. This review draws on recent work to define the role of Agr during bacteremia and explain why the loss of this major virulence regulator is sometimes a price worth paying for S. aureus.