TY - JOUR
T1 - Regulation of Virulence in Staphylococcus aureus
T2 - Molecular Mechanisms and Remaining Puzzles
AU - Wang, Boyuan
AU - Muir, Tom W.
N1 - Funding Information:
This work was supported by NIH grants AI042783 and GM095880 .
Publisher Copyright:
© 2016 Elsevier Ltd All rights reserved.
PY - 2016/2/18
Y1 - 2016/2/18
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chembiol.2016.01.004
DO - 10.1016/j.chembiol.2016.01.004
M3 - Review article
C2 - 26971873
AN - SCOPUS:84965017170
SN - 2451-9448
VL - 23
SP - 214
EP - 224
JO - Cell Chemical Biology
JF - Cell Chemical Biology
IS - 2
ER -