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

Research output: Contribution to journalJournal articleResearchpeer-review

452 Downloads (Pure)

Abstract

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
Volume8
Issue number1
Number of pages11
ISSN2045-2322
DOIs
Publication statusPublished - 2018

Bibliographical note

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Fingerprint

Dive into the research topics of 'Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing'. Together they form a unique fingerprint.

Cite this