Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783377151749259264 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6272417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liubingrun quercitrinaninhibitorofsortaseainterfereswiththeadhesionofstaphylococcalaureus AT chenfuguang quercitrinaninhibitorofsortaseainterfereswiththeadhesionofstaphylococcalaureus AT bichongwei quercitrinaninhibitorofsortaseainterfereswiththeadhesionofstaphylococcalaureus AT wanglin quercitrinaninhibitorofsortaseainterfereswiththeadhesionofstaphylococcalaureus AT zhongxiaobo quercitrinaninhibitorofsortaseainterfereswiththeadhesionofstaphylococcalaureus AT caihongjun quercitrinaninhibitorofsortaseainterfereswiththeadhesionofstaphylococcalaureus AT dengxuming quercitrinaninhibitorofsortaseainterfereswiththeadhesionofstaphylococcalaureus AT niuxiaodi quercitrinaninhibitorofsortaseainterfereswiththeadhesionofstaphylococcalaureus AT wangdacheng quercitrinaninhibitorofsortaseainterfereswiththeadhesionofstaphylococcalaureus |