Regulation of Virulence in Staphylococcus aureus: Molecular Mechanisms and Remaining Puzzles.

TitleRegulation of Virulence in Staphylococcus aureus: Molecular Mechanisms and Remaining Puzzles.
Publication TypeJournal Article
Year of Publication2016
AuthorsWang, B, Muir, TW
JournalCell Chem Biol
Volume23
Issue2
Pagination214-224
Date Published2016 Feb 18
ISSN2451-9448
KeywordsBacterial Proteins, Biological Products, Models, Molecular, Molecular Conformation, Protein Kinases, Staphylococcus aureus, Virulence
Abstract

<p>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.</p>

DOI10.1016/j.chembiol.2016.01.004
Alternate JournalCell Chem Biol
PubMed ID26971873
PubMed Central IDPMC4847544
Grant ListR01 AI042783 / AI / NIAID NIH HHS / United States
R01 GM095880 / GM / NIGMS NIH HHS / United States
AI042783 / AI / NIAID NIH HHS / United States
GM095880 / GM / NIGMS NIH HHS / United States