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

Boyuan Wang, Aishan Zhao, Qian Xie, Paul Dominic Olinares, Brian T. Chait, Richard P. Novick, Tom W. Muir

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)76-86
Number of pages11
JournalCell Chemical Biology
Issue number1
StatePublished - Jan 19 2017

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Molecular Medicine
  • Molecular Biology
  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology


  • Staphylococcus aureus
  • agr
  • allelic variation
  • constitutive mutant
  • input-response property
  • nanodisc
  • phospho-transfer
  • quorum sensing
  • transmembrane histidine kinase
  • two-component signaling


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