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Quercitrin, an Inhibitor of Sortase A, Interferes with the Adhesion of Staphylococcal aureus

Sortase A (SrtA) is a cysteine transpeptidase of most Gram-positive bacteria that is responsible for the anchorage of many surface protein virulence factors to the cell wall layer. SrtA mutants are unable to display surface proteins and are defective in the establishment of infections without affect...

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Autores principales: Liu, Bingrun, Chen, Fuguang, Bi, Chongwei, Wang, Lin, Zhong, Xiaobo, Cai, Hongjun, Deng, Xuming, Niu, Xiaodi, Wang, Dacheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272417/
https://www.ncbi.nlm.nih.gov/pubmed/25871372
http://dx.doi.org/10.3390/molecules20046533
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author Liu, Bingrun
Chen, Fuguang
Bi, Chongwei
Wang, Lin
Zhong, Xiaobo
Cai, Hongjun
Deng, Xuming
Niu, Xiaodi
Wang, Dacheng
author_facet Liu, Bingrun
Chen, Fuguang
Bi, Chongwei
Wang, Lin
Zhong, Xiaobo
Cai, Hongjun
Deng, Xuming
Niu, Xiaodi
Wang, Dacheng
author_sort Liu, Bingrun
collection PubMed
description Sortase A (SrtA) is a cysteine transpeptidase of most Gram-positive bacteria that is responsible for the anchorage of many surface protein virulence factors to the cell wall layer. SrtA mutants are unable to display surface proteins and are defective in the establishment of infections without affecting microbial viability. In this study, we report that quercitrin (QEN), a natural compound that does not affect Staphylococcus aureus growth, can inhibit the catalytic activity of SrtA in fibrinogen (Fg) cell-clumping and immobilized fibronectin (Fn) adhesion assays. Molecular dynamics simulations and mutagenesis assays suggest that QEN binds to the binding sites of the SrtA G167A and V193A mutants. These findings indicate that QEN is a potential lead compound for the development of new anti-virulence agents against S. aureus infections.
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spelling pubmed-62724172018-12-03 Quercitrin, an Inhibitor of Sortase A, Interferes with the Adhesion of Staphylococcal aureus Liu, Bingrun Chen, Fuguang Bi, Chongwei Wang, Lin Zhong, Xiaobo Cai, Hongjun Deng, Xuming Niu, Xiaodi Wang, Dacheng Molecules Article Sortase A (SrtA) is a cysteine transpeptidase of most Gram-positive bacteria that is responsible for the anchorage of many surface protein virulence factors to the cell wall layer. SrtA mutants are unable to display surface proteins and are defective in the establishment of infections without affecting microbial viability. In this study, we report that quercitrin (QEN), a natural compound that does not affect Staphylococcus aureus growth, can inhibit the catalytic activity of SrtA in fibrinogen (Fg) cell-clumping and immobilized fibronectin (Fn) adhesion assays. Molecular dynamics simulations and mutagenesis assays suggest that QEN binds to the binding sites of the SrtA G167A and V193A mutants. These findings indicate that QEN is a potential lead compound for the development of new anti-virulence agents against S. aureus infections. MDPI 2015-04-13 /pmc/articles/PMC6272417/ /pubmed/25871372 http://dx.doi.org/10.3390/molecules20046533 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Bingrun
Chen, Fuguang
Bi, Chongwei
Wang, Lin
Zhong, Xiaobo
Cai, Hongjun
Deng, Xuming
Niu, Xiaodi
Wang, Dacheng
Quercitrin, an Inhibitor of Sortase A, Interferes with the Adhesion of Staphylococcal aureus
title Quercitrin, an Inhibitor of Sortase A, Interferes with the Adhesion of Staphylococcal aureus
title_full Quercitrin, an Inhibitor of Sortase A, Interferes with the Adhesion of Staphylococcal aureus
title_fullStr Quercitrin, an Inhibitor of Sortase A, Interferes with the Adhesion of Staphylococcal aureus
title_full_unstemmed Quercitrin, an Inhibitor of Sortase A, Interferes with the Adhesion of Staphylococcal aureus
title_short Quercitrin, an Inhibitor of Sortase A, Interferes with the Adhesion of Staphylococcal aureus
title_sort quercitrin, an inhibitor of sortase a, interferes with the adhesion of staphylococcal aureus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272417/
https://www.ncbi.nlm.nih.gov/pubmed/25871372
http://dx.doi.org/10.3390/molecules20046533
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