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Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections
Novel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is know...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481386/ https://www.ncbi.nlm.nih.gov/pubmed/26111644 http://dx.doi.org/10.1038/srep11596 |
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author | Thangamani, Shankar Younis, Waleed Seleem, Mohamed N. |
author_facet | Thangamani, Shankar Younis, Waleed Seleem, Mohamed N. |
author_sort | Thangamani, Shankar |
collection | PubMed |
description | Novel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is known to be clinically safe and has a well-known pharmacology profile. It has shown potent bactericidal activity against multidrug-resistant clinical isolates of staphylococcus aureus, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA). We demonstrated that ebselen acts through inhibition of protein synthesis and subsequently inhibited toxin production in MRSA. Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms. The therapeutic efficacy of ebselen was evaluated in a mouse model of staphylococcal skin infections. Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions. Furthermore, it acts synergistically with traditional antimicrobials. This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections. |
format | Online Article Text |
id | pubmed-4481386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44813862015-06-30 Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections Thangamani, Shankar Younis, Waleed Seleem, Mohamed N. Sci Rep Article Novel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is known to be clinically safe and has a well-known pharmacology profile. It has shown potent bactericidal activity against multidrug-resistant clinical isolates of staphylococcus aureus, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA). We demonstrated that ebselen acts through inhibition of protein synthesis and subsequently inhibited toxin production in MRSA. Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms. The therapeutic efficacy of ebselen was evaluated in a mouse model of staphylococcal skin infections. Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions. Furthermore, it acts synergistically with traditional antimicrobials. This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections. Nature Publishing Group 2015-06-26 /pmc/articles/PMC4481386/ /pubmed/26111644 http://dx.doi.org/10.1038/srep11596 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Thangamani, Shankar Younis, Waleed Seleem, Mohamed N. Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections |
title | Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections |
title_full | Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections |
title_fullStr | Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections |
title_full_unstemmed | Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections |
title_short | Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections |
title_sort | repurposing ebselen for treatment of multidrug-resistant staphylococcal infections |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481386/ https://www.ncbi.nlm.nih.gov/pubmed/26111644 http://dx.doi.org/10.1038/srep11596 |
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