Research Progress on Antivirulence Agents Targeting the Accessory Gene Regulator (Agr) System of Staphylococcus Aureus

Lingwei Chen,1,2 Mintao Huang,1,2 Ying Chen,1,2 Yanzhen Lin,1,2 Yanguang Cong1– 4 1Dongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, People’s Republic of China; 2Department of Clinical Laboratory, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, People’s Republic of China; 3Dongguan Key Laboratory of Sepsis Translational Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523710, People’s Republic of China; 4Guangdong Provincial Clinical Research Center for Laboratory Medicine, Guangzhou, 510280, People’s Republic of ChinaCorrespondence: Yanguang Cong, Email [email protected]: 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