Discovery of quorum quenchers targeting the membrane-embedded sensor domain of the<i>Staphylococcus aureus</i>receptor histidine kinase, AgrC
Qian Xie, Mareike M. Wiedmann, Aishan Zhao, Ivelisse Rodriguez Pagan, Richard P. Novick, Hiroaki Suga, Tom W. Muir
Abstract
We combined mRNA display technology with lipid-nanodisc based selections and identified high-affinity ligands targeting the integral membrane sensor domain of the histidine kinase AgrC as potent inhibitors of Staphylococcus aureus quorum sensing-modulated virulence. Our study highlights the potential of this integrated approach for identifying functional modulators of integral membrane proteins.
Topics & Concepts
Histidine kinaseQuorum sensingStaphylococcus aureusChemistryHistidineKinaseBiochemistryBiophysicsCombinatorial chemistryBiologyBacteriaEnzymeGeneticsGeneVirulenceAntimicrobial Resistance in StaphylococcusBiochemical and Structural CharacterizationBacterial biofilms and quorum sensing