An insight into pleiotropic regulators Agr and Sar: molecular probes paving the new way for antivirulent therapy

Abstract

Staphylococcus aureus pathogenesis is an intricate process involving a diverse array of extracellular proteins, biofilm and cell wall components that are coordinately expressed in different stages of infection. The expression of two divergent loci, agr and sar, is increasingly recognized as a key regulator of virulence in S. aureus, and there is mounting evidence for the role of these loci in staphylococcal infections. The functional agr regulon is critical for the production of virulence factors, including α, β and δ hemolysins. The sar locus encodes SarA protein, which regulates the expression of cell wall-associated and certain extracellular proteins in agr-dependent and agr-independent pathways. Multidrug-resistant S. aureus is a leading cause of morbidity and mortality in the world and its management, especially in community-acquired methicillin-resistant S. aureus infections, has evolved comparatively little. In particular, no novel targets have been incorporated into its treatment to date. Hence, these loci appear to be the most significant and are currently at the attention of intense investigation regarding their therapeutic prospects.