Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing

Georgia Karathanasi, Martin Saxtorph Bojer, Mara Baldry, Bardur Andreson Johannessen, Sanne Wolff, Ines Greco, Mogens Kilstrup, Paul Robert Hansen, Hanne Ingmer*

*Corresponding author for this work

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Staphylococcus aureus is an important pathogen causing infections in humans and animals. Increasing problems with antimicrobial resistance has prompted the development of alternative treatment strategies, including antivirulence approaches targeting virulence regulation such as the agr quorum sensing system. agr is naturally induced by cyclic auto-inducing peptides (AIPs) binding to the AgrC receptor and cyclic peptide inhibitors have been identified competing with AIP binding to AgrC. Here, we disclose that small, linear peptidomimetics can act as specific and potent inhibitors of the S. aureus agr system via intercepting AIP-AgrC signal interaction at low micromolar concentrations. The corresponding linear peptide did not have this ability. This is the first report of a linear peptide-like molecule that interferes with agr activation by competitive binding to AgrC. Prospectively, these peptidomimetics may be valuable starting scaffolds for the development of new inhibitors of staphylococcal quorum sensing and virulence gene expression.
Original languageEnglish
Article number3562
JournalScientific Reports
Issue number1
Number of pages11
Publication statusPublished - 2018

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