title: Regulation of Virulence in Staphylococcus aureus: Molecular Mechanisms and Remaining Puzzles.
abstract: The agr locus encodes a quorum-sensing (QS) circuit required for the virulence of a spectrum of Gram-positive pathogens and is, therefore, regarded as an important target for the development of chemotherapeutics. In recent years, many of the biochemical events in the Staphylococcus aureus agr circuit have been reconstituted and subject to quantitative analysis in vitro. This work, in conjunction with structural studies on several key players in the signaling circuit, has furnished mechanistic insights into the regulation and evolution of the agr QS system. Here, we review this progress and discuss the remaining open questions in the area. We also highlight advances in the discovery of small-molecule agr modulators and how the newly available biochemical and structural information might be leveraged for the design of next-generation therapeutics targeting the agr system.
authors.affiliation: Frick Chemistry Laboratory, Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA; Graduate Program, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Boyuan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Frick Chemistry Laboratory, Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA. Electronic address: muir@princeton.edu.
authors.forename: Tom W
authors.initials: TW
authors.lastname: Muir
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D001688:Biological Products; D011494:Protein Kinases; C531166:AgrC protein, Staphylococcus