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Cell Chem Biol. 2017 Jan 19;24(1):76-86. doi: 10.1016/j.chembiol.2016.12.008. Epub 2017 Jan 5.

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

Author information

1
Department of Chemistry, Frick Chemistry Laboratory, Princeton University, Washington Road, Princeton, NJ 08544-0015, USA; Graduate Program, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
2
Department of Chemistry, Frick Chemistry Laboratory, Princeton University, Washington Road, Princeton, NJ 08544-0015, USA.
3
Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
4
Department of Microbiology, Skirball Institute, NYU Medical Center, 540-562 First Avenue, New York, NY 10016, USA.
5
Department of Chemistry, Frick Chemistry Laboratory, Princeton University, Washington Road, Princeton, NJ 08544-0015, USA. Electronic address: muir@princeton.edu.

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.

KEYWORDS:

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

PMID:
28065658
PMCID:
PMC5697745
DOI:
10.1016/j.chembiol.2016.12.008
[Indexed for MEDLINE]
Free PMC Article

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