Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing

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 quor...

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Autores principales:	Georgia Karathanasi, Martin Saxtorph Bojer, Mara Baldry, Bárdur Andréson Johannessen, Sanne Wolff, Ines Greco, Mogens Kilstrup, Paul Robert Hansen, Hanne Ingmer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e8f658bf9a84532b016d37cafc5623a
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spelling	oai:doaj.org-article:8e8f658bf9a84532b016d37cafc5623a2021-12-02T15:08:44ZLinear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing10.1038/s41598-018-21951-42045-2322https://doaj.org/article/8e8f658bf9a84532b016d37cafc5623a2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21951-4https://doaj.org/toc/2045-2322Abstract 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.Georgia KarathanasiMartin Saxtorph BojerMara BaldryBárdur Andréson JohannessenSanne WolffInes GrecoMogens KilstrupPaul Robert HansenHanne IngmerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Georgia Karathanasi Martin Saxtorph Bojer Mara Baldry Bárdur Andréson Johannessen Sanne Wolff Ines Greco Mogens Kilstrup Paul Robert Hansen Hanne Ingmer Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing
description	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.
format	article
author	Georgia Karathanasi Martin Saxtorph Bojer Mara Baldry Bárdur Andréson Johannessen Sanne Wolff Ines Greco Mogens Kilstrup Paul Robert Hansen Hanne Ingmer
author_facet	Georgia Karathanasi Martin Saxtorph Bojer Mara Baldry Bárdur Andréson Johannessen Sanne Wolff Ines Greco Mogens Kilstrup Paul Robert Hansen Hanne Ingmer
author_sort	Georgia Karathanasi
title	Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing
title_short	Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing
title_full	Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing
title_fullStr	Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing
title_full_unstemmed	Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing
title_sort	linear peptidomimetics as potent antagonists of staphylococcus aureus agr quorum sensing
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8e8f658bf9a84532b016d37cafc5623a
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Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing

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