title: Functional Plasticity of the AgrC Receptor Histidine Kinase Required for Staphylococcal Virulence.
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.
authors.affiliation: 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.
authors.forename: Boyuan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Frick Chemistry Laboratory, Princeton University, Washington Road, Princeton, NJ 08544-0015, USA.
authors.forename: Aishan
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Department of Chemistry, Frick Chemistry Laboratory, Princeton University, Washington Road, Princeton, NJ 08544-0015, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Paul Dominic
authors.initials: PD
authors.lastname: Olinares
authors.affiliation: Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chait
authors.affiliation: Department of Microbiology, Skirball Institute, NYU Medical Center, 540-562 First Avenue, New York, NY 10016, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Novick
authors.affiliation: Department of Chemistry, Frick Chemistry Laboratory, Princeton University, Washington Road, Princeton, NJ 08544-0015, USA. Electronic address: muir@princeton.edu.
authors.forename: Tom W
authors.initials: TW
authors.lastname: Muir
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D053038:Quorum Sensing; D013211:Staphylococcus aureus / Q000201:enzymology / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D011494:Protein Kinases; C531166:AgrC protein, Staphylococcus
keywords: Staphylococcus aureus; agr; allelic variation; constitutive mutant; input-response property; nanodisc; phospho-transfer; quorum sensing; transmembrane histidine kinase; two-component signaling