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Topical Therapeutic Efficacy of Ebselen Against Multidrug-Resistant Staphylococcus aureus LT-1 Targeting Thioredoxin Reductase

As a thiol-dependent enzyme, thioredoxin reductase (TrxR) is a promising antibacterial drug target. Ebselen, an organo-selenium with well-characterized toxicology and pharmacology, was recently reported to have potent antibacterial activity against Staphylococcus aureus. In this paper, we demonstrat...

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Autores principales: Dong, Chuanjiang, Zhou, Jingxuan, Wang, Peng, Li, Tao, Zhao, Ying, Ren, Xiaoyuan, Lu, Jun, Wang, Jun, Holmgren, Arne, Zou, Lili
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974526/
https://www.ncbi.nlm.nih.gov/pubmed/32010088
http://dx.doi.org/10.3389/fmicb.2019.03016
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author Dong, Chuanjiang
Zhou, Jingxuan
Wang, Peng
Li, Tao
Zhao, Ying
Ren, Xiaoyuan
Lu, Jun
Wang, Jun
Holmgren, Arne
Zou, Lili
author_facet Dong, Chuanjiang
Zhou, Jingxuan
Wang, Peng
Li, Tao
Zhao, Ying
Ren, Xiaoyuan
Lu, Jun
Wang, Jun
Holmgren, Arne
Zou, Lili
author_sort Dong, Chuanjiang
collection PubMed
description As a thiol-dependent enzyme, thioredoxin reductase (TrxR) is a promising antibacterial drug target. Ebselen, an organo-selenium with well-characterized toxicology and pharmacology, was recently reported to have potent antibacterial activity against Staphylococcus aureus. In this paper, we demonstrated that ebselen has strong bactericidal activity against multidrug-resistant (MDR) S. aureus based on taking TrxR as a major target and disruption of the redox microenvironment. Further, the topical therapeutic efficacy of ebselen for staphylococcal skin infections was assessed in a rat model. Treatment with ebselen significantly reduced the bacterial load and the expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) in S. aureus skin lesions; further, wound healing and pathological changes were obvious improved in ebselen-treated rats compare to controls. Finally, ebselen was found to sensitize S. aureus to curcumin, which may be due to their synergistic effects in inhibiting bacterial TrxR. Altogether, ebselen is an effective topical antibacterial agent in animal model of MDR S. aureus LT-1 skin infection. This may lay the foundation for further analysis and development of ebselen as an antibacterial agent for topical treatment of MDR staphylococcal infections.
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spelling pubmed-69745262020-01-31 Topical Therapeutic Efficacy of Ebselen Against Multidrug-Resistant Staphylococcus aureus LT-1 Targeting Thioredoxin Reductase Dong, Chuanjiang Zhou, Jingxuan Wang, Peng Li, Tao Zhao, Ying Ren, Xiaoyuan Lu, Jun Wang, Jun Holmgren, Arne Zou, Lili Front Microbiol Microbiology As a thiol-dependent enzyme, thioredoxin reductase (TrxR) is a promising antibacterial drug target. Ebselen, an organo-selenium with well-characterized toxicology and pharmacology, was recently reported to have potent antibacterial activity against Staphylococcus aureus. In this paper, we demonstrated that ebselen has strong bactericidal activity against multidrug-resistant (MDR) S. aureus based on taking TrxR as a major target and disruption of the redox microenvironment. Further, the topical therapeutic efficacy of ebselen for staphylococcal skin infections was assessed in a rat model. Treatment with ebselen significantly reduced the bacterial load and the expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) in S. aureus skin lesions; further, wound healing and pathological changes were obvious improved in ebselen-treated rats compare to controls. Finally, ebselen was found to sensitize S. aureus to curcumin, which may be due to their synergistic effects in inhibiting bacterial TrxR. Altogether, ebselen is an effective topical antibacterial agent in animal model of MDR S. aureus LT-1 skin infection. This may lay the foundation for further analysis and development of ebselen as an antibacterial agent for topical treatment of MDR staphylococcal infections. Frontiers Media S.A. 2020-01-15 /pmc/articles/PMC6974526/ /pubmed/32010088 http://dx.doi.org/10.3389/fmicb.2019.03016 Text en Copyright © 2020 Dong, Zhou, Wang, Li, Zhao, Ren, Lu, Wang, Holmgren and Zou. 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 Microbiology
Dong, Chuanjiang
Zhou, Jingxuan
Wang, Peng
Li, Tao
Zhao, Ying
Ren, Xiaoyuan
Lu, Jun
Wang, Jun
Holmgren, Arne
Zou, Lili
Topical Therapeutic Efficacy of Ebselen Against Multidrug-Resistant Staphylococcus aureus LT-1 Targeting Thioredoxin Reductase
title Topical Therapeutic Efficacy of Ebselen Against Multidrug-Resistant Staphylococcus aureus LT-1 Targeting Thioredoxin Reductase
title_full Topical Therapeutic Efficacy of Ebselen Against Multidrug-Resistant Staphylococcus aureus LT-1 Targeting Thioredoxin Reductase
title_fullStr Topical Therapeutic Efficacy of Ebselen Against Multidrug-Resistant Staphylococcus aureus LT-1 Targeting Thioredoxin Reductase
title_full_unstemmed Topical Therapeutic Efficacy of Ebselen Against Multidrug-Resistant Staphylococcus aureus LT-1 Targeting Thioredoxin Reductase
title_short Topical Therapeutic Efficacy of Ebselen Against Multidrug-Resistant Staphylococcus aureus LT-1 Targeting Thioredoxin Reductase
title_sort topical therapeutic efficacy of ebselen against multidrug-resistant staphylococcus aureus lt-1 targeting thioredoxin reductase
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974526/
https://www.ncbi.nlm.nih.gov/pubmed/32010088
http://dx.doi.org/10.3389/fmicb.2019.03016
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