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Published on: February 19, 2019
Functional Plasticity of the AgrC Receptor Histidine Kinase Required for Staphylococcal Virulence
Boyuan Wang1, Aishan Zhao2, Qian Xie2
1Department 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.
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.
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