Accessory gene regulator (agr) system (agr)

The Accessory gene regulator (agr) system is the master quorum-sensing apparatus in Staphylococcus aureus, regulating the transition from a colonizing to an invasive phenotype (Novick & Geisinger, 2008). It consists of the agrACDB operon, which produces an autoinducing peptide (AIP) that, upon reaching a threshold concentration, activates the AgrC-AgrA two-component signaling pathway (Otto, 2004). This activation triggers the transcription of RNAIII, the system's primary effector, which upregulates the production of secreted toxins (e.g., alpha-hemolysin) and enzymes while downregulating surface adhesins. The agr system is a significant target for anti-virulence therapies, such as Savirin and Solonamide B, which aim to suppress bacterial toxicity without exerting the strong selective pressure of traditional antibiotics (Gordon et al., 2013). However, the system's role is complex; agr dysfunction is associated with increased cell wall peptidoglycan thickness and the development of vancomycin-intermediate S. aureus (VISA) strains (Tan et al., 2018). Furthermore, loss of agr activity can promote biofilm formation and lead to persistent, chronic infections, presenting a major challenge for therapeutic intervention (Nielsen et al., 2014).

Other names

agr locusagr quorum sensing systemAccessory gene regulatoragrACDB operon

Inhibition of the AgrC-AgrA two-component signaling pathway to suppress the transition from a colonizing to an invasive phenotype by downregulating virulence factors like alpha-hemolysin and phenol-soluble modulins.