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Discovery of Potential Anti-infective Therapy Targeting Glutamine Synthetase in Staphylococcus xylosus

Glutamine synthetase (GS), which catalyzes the production of glutamine, plays essential roles in most biological growth and biofilm formation, suggesting that GS may be used as a promising target for antibacterial therapy. We asked whether a GS inhibitor could be found as an anti-infective agent of...

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Autores principales: Cui, Wen-Qiang, Qu, Qian-Wei, Wang, Jin-Peng, Bai, Jing-Wen, Bello-Onaghise, God'spower, Li, Yu-Ang, Zhou, Yong-Hui, Chen, Xing-Ru, Liu, Xin, Zheng, Si-Di, Xing, Xiao-Xu, Eliphaz, Nsabimana, Li, Yan-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558069/
https://www.ncbi.nlm.nih.gov/pubmed/31214565
http://dx.doi.org/10.3389/fchem.2019.00381
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author Cui, Wen-Qiang
Qu, Qian-Wei
Wang, Jin-Peng
Bai, Jing-Wen
Bello-Onaghise, God'spower
Li, Yu-Ang
Zhou, Yong-Hui
Chen, Xing-Ru
Liu, Xin
Zheng, Si-Di
Xing, Xiao-Xu
Eliphaz, Nsabimana
Li, Yan-Hua
author_facet Cui, Wen-Qiang
Qu, Qian-Wei
Wang, Jin-Peng
Bai, Jing-Wen
Bello-Onaghise, God'spower
Li, Yu-Ang
Zhou, Yong-Hui
Chen, Xing-Ru
Liu, Xin
Zheng, Si-Di
Xing, Xiao-Xu
Eliphaz, Nsabimana
Li, Yan-Hua
author_sort Cui, Wen-Qiang
collection PubMed
description Glutamine synthetase (GS), which catalyzes the production of glutamine, plays essential roles in most biological growth and biofilm formation, suggesting that GS may be used as a promising target for antibacterial therapy. We asked whether a GS inhibitor could be found as an anti-infective agent of Staphylococcus xylosus (S. xylosus). Here, computational prediction followed by experimental testing was used to characterize GS. Sorafenib was finally determined through computational prediction. In vitro experiments showed that sorafenib has an inhibitory effect on the growth of S. xylosus by competitively occupying the active site of GS, and the minimum inhibitory concentration was 4 mg/L. In vivo experiments also proved that treatment with sorafenib significantly reduced the levels of TNF-α and IL-6 in breast tissue from mice mastitis, which was further confirmed by histopathology examination. These findings indicated that sorafenib could be utilized as an anti-infective agent for the treatment of infections caused by S. xylosus.
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spelling pubmed-65580692019-06-18 Discovery of Potential Anti-infective Therapy Targeting Glutamine Synthetase in Staphylococcus xylosus Cui, Wen-Qiang Qu, Qian-Wei Wang, Jin-Peng Bai, Jing-Wen Bello-Onaghise, God'spower Li, Yu-Ang Zhou, Yong-Hui Chen, Xing-Ru Liu, Xin Zheng, Si-Di Xing, Xiao-Xu Eliphaz, Nsabimana Li, Yan-Hua Front Chem Chemistry Glutamine synthetase (GS), which catalyzes the production of glutamine, plays essential roles in most biological growth and biofilm formation, suggesting that GS may be used as a promising target for antibacterial therapy. We asked whether a GS inhibitor could be found as an anti-infective agent of Staphylococcus xylosus (S. xylosus). Here, computational prediction followed by experimental testing was used to characterize GS. Sorafenib was finally determined through computational prediction. In vitro experiments showed that sorafenib has an inhibitory effect on the growth of S. xylosus by competitively occupying the active site of GS, and the minimum inhibitory concentration was 4 mg/L. In vivo experiments also proved that treatment with sorafenib significantly reduced the levels of TNF-α and IL-6 in breast tissue from mice mastitis, which was further confirmed by histopathology examination. These findings indicated that sorafenib could be utilized as an anti-infective agent for the treatment of infections caused by S. xylosus. Frontiers Media S.A. 2019-06-04 /pmc/articles/PMC6558069/ /pubmed/31214565 http://dx.doi.org/10.3389/fchem.2019.00381 Text en Copyright © 2019 Cui, Qu, Wang, Bai, Bello-Onaghise, Li, Zhou, Chen, Liu, Zheng, Xing, Eliphaz and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Cui, Wen-Qiang
Qu, Qian-Wei
Wang, Jin-Peng
Bai, Jing-Wen
Bello-Onaghise, God'spower
Li, Yu-Ang
Zhou, Yong-Hui
Chen, Xing-Ru
Liu, Xin
Zheng, Si-Di
Xing, Xiao-Xu
Eliphaz, Nsabimana
Li, Yan-Hua
Discovery of Potential Anti-infective Therapy Targeting Glutamine Synthetase in Staphylococcus xylosus
title Discovery of Potential Anti-infective Therapy Targeting Glutamine Synthetase in Staphylococcus xylosus
title_full Discovery of Potential Anti-infective Therapy Targeting Glutamine Synthetase in Staphylococcus xylosus
title_fullStr Discovery of Potential Anti-infective Therapy Targeting Glutamine Synthetase in Staphylococcus xylosus
title_full_unstemmed Discovery of Potential Anti-infective Therapy Targeting Glutamine Synthetase in Staphylococcus xylosus
title_short Discovery of Potential Anti-infective Therapy Targeting Glutamine Synthetase in Staphylococcus xylosus
title_sort discovery of potential anti-infective therapy targeting glutamine synthetase in staphylococcus xylosus
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558069/
https://www.ncbi.nlm.nih.gov/pubmed/31214565
http://dx.doi.org/10.3389/fchem.2019.00381
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