Abstract: With global spread of drug-resistant strains such as methicillin-resistant Staphylococcus aureus , conventional antimicrobial strategies face significant challenges, which prompt the development of antiinfective agents with alternative strategies. The antivirulence approach targets bacterial virulence factors without directly killing the bacteria. The accessory gene regulator (Agr) system, a central quorum-sensing pathway in S. aureus , represents a primary target for such therapies. However, inhibition of the Agr system presents a dual nature: while it attenuates acute virulence, it may inadvertently promote biofilm formation and poses potential therapeutic trade-offs. This review provides an overview of the Agr system structure and functional mechanisms alongside recent advances in synthetic and natural quorum sensing inhibitors targeting the Agr system in S. aureus . By regulating primary virulence factors, this system serves as an ideal target for antivirulence therapies. Disrupting Agr can reduce pathogenicity without affecting bacterial growth. Current researches suggest that the Agr inhibitors hold significant potential as novel therapeutics, though their clinical application requires careful consideration of the dual effects. Keywords: quorum sensing, Agr system, antivirulence, Agr inhibitors, quenching antibodies
Chen et al. (Sun,) studied this question.