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Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A

The intractability of bacterial resistance presents a dilemma for therapies against Staphylococcus aureus (S. aureus) infection. Effective anti-virulence strategies are urgently needed, reflecting the proliferation of resistant strains. Inhibitors of sortase A (SrtA), enzymes that anchor virulence-r...

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Autores principales: Zhang, Bing, Wang, Xiyan, Wang, Lin, Chen, Shuiye, Shi, Dongxue, Wang, Hongsu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273746/
https://www.ncbi.nlm.nih.gov/pubmed/27792196
http://dx.doi.org/10.3390/molecules21111428
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author Zhang, Bing
Wang, Xiyan
Wang, Lin
Chen, Shuiye
Shi, Dongxue
Wang, Hongsu
author_facet Zhang, Bing
Wang, Xiyan
Wang, Lin
Chen, Shuiye
Shi, Dongxue
Wang, Hongsu
author_sort Zhang, Bing
collection PubMed
description The intractability of bacterial resistance presents a dilemma for therapies against Staphylococcus aureus (S. aureus) infection. Effective anti-virulence strategies are urgently needed, reflecting the proliferation of resistant strains. Inhibitors of sortase A (SrtA), enzymes that anchor virulence-related surface proteins, are regarded as promising candidates for countermeasures against bacterial infections. In the present study, the inhibitory effect of dryocrassin ABBA (ABBA) against SrtA and its molecular basis has been examined. Fluorescence resonance energy transfer (FRET) assays were used to determine the inhibitory activity of ABBA against SrtA. To identify the mechanism underlying this activity, molecular dynamics simulations and mutagenesis assays were applied, and the results revealed that the direct engagement of SrtA via ABBA through binding to V166 and V168 significantly attenuated the catalytic activity of SrtA. Taken together, these findings indicated that ABBA is a potential novel antimicrobial agent for S. aureus infection via targeting SrtA.
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spelling pubmed-62737462018-12-28 Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A Zhang, Bing Wang, Xiyan Wang, Lin Chen, Shuiye Shi, Dongxue Wang, Hongsu Molecules Article The intractability of bacterial resistance presents a dilemma for therapies against Staphylococcus aureus (S. aureus) infection. Effective anti-virulence strategies are urgently needed, reflecting the proliferation of resistant strains. Inhibitors of sortase A (SrtA), enzymes that anchor virulence-related surface proteins, are regarded as promising candidates for countermeasures against bacterial infections. In the present study, the inhibitory effect of dryocrassin ABBA (ABBA) against SrtA and its molecular basis has been examined. Fluorescence resonance energy transfer (FRET) assays were used to determine the inhibitory activity of ABBA against SrtA. To identify the mechanism underlying this activity, molecular dynamics simulations and mutagenesis assays were applied, and the results revealed that the direct engagement of SrtA via ABBA through binding to V166 and V168 significantly attenuated the catalytic activity of SrtA. Taken together, these findings indicated that ABBA is a potential novel antimicrobial agent for S. aureus infection via targeting SrtA. MDPI 2016-10-26 /pmc/articles/PMC6273746/ /pubmed/27792196 http://dx.doi.org/10.3390/molecules21111428 Text en © 2016 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 (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Bing
Wang, Xiyan
Wang, Lin
Chen, Shuiye
Shi, Dongxue
Wang, Hongsu
Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A
title Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A
title_full Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A
title_fullStr Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A
title_full_unstemmed Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A
title_short Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A
title_sort molecular mechanism of the flavonoid natural product dryocrassin abba against staphylococcus aureus sortase a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273746/
https://www.ncbi.nlm.nih.gov/pubmed/27792196
http://dx.doi.org/10.3390/molecules21111428
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