Functional Plasticity of the AgrC Receptor Histidine Kinase Required for Staphylococcal Virulence.

TitleFunctional Plasticity of the AgrC Receptor Histidine Kinase Required for Staphylococcal Virulence.
Publication TypeJournal Article
Year of Publication2017
AuthorsWang, B, Zhao, A, Xie, Q, Olinares, PDominic, Chait, BT, Novick, RP, Muir, TW
JournalCell Chem Biol
Volume24
Issue1
Pagination76-86
Date Published2017 Jan 19
ISSN2451-9456
Abstract

Staphylococcus aureus employs the receptor histidine kinase (RHK), AgrC, to detect quorum-sensing (QS) pheromones, the autoinducer peptides (AIPs), which regulate the virulence of the bacterium. Variation in the QS circuit divides S. aureus into four subgroups, each producing a specific AIP-AgrC pair. While the timing of QS induction is known to differ among these subgroups, the molecular basis of this phenomenon is unknown. Here, we report the successful reconstitution of several AgrC variants and show that the agonist-induced activity of the receptors varies in a manner that accounts for these temporal differences in QS induction. Our studies also reveal a key regulatory hotspot on AgrC that controls the basal activity of RHK as well as the responsiveness of the system to ligand inputs. Collectively, these studies offer insights into the capacity of the RHK for adaptive evolution.

DOI10.1016/j.chembiol.2016.12.008
Alternate JournalCell Chem Biol
PubMed ID28065658