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Anti-biofilm and Anti-Virulence Efficacy of Celastrol Against Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is a multi-drug resistant opportunistic pathogen that causes nosocomial infections in immunocompromised patients. This pathogen is difficult to treat owing to its intrinsic multidrug resistance and ability to form antimicrobial-tolerant biofilms. In the present study, we...

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Autores principales: Kim, Hye-Rim, Lee, Dongsup, Eom, Yong-Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930464/
https://www.ncbi.nlm.nih.gov/pubmed/29725253
http://dx.doi.org/10.7150/ijms.23924
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author Kim, Hye-Rim
Lee, Dongsup
Eom, Yong-Bin
author_facet Kim, Hye-Rim
Lee, Dongsup
Eom, Yong-Bin
author_sort Kim, Hye-Rim
collection PubMed
description Stenotrophomonas maltophilia is a multi-drug resistant opportunistic pathogen that causes nosocomial infections in immunocompromised patients. This pathogen is difficult to treat owing to its intrinsic multidrug resistance and ability to form antimicrobial-tolerant biofilms. In the present study, we aimed to assess the potential use of celastrol as a novel anti-biofilm and/or anti-virulence agent against S. maltophilia. Results showed that celastrol at its sub-inhibitory doses decreased biofilm formation and disrupt the established biofilms produced by S. maltophilia. Celastrol-induced decrease in biofilm formation was dose-dependent based on the results of the microtiter plate biofilm assays and confocal laser scanning microscopy. In addition, our data validated the anti-virulence efficacy of celastrol, wherein it significantly interfered with the production of protease and motility of S. maltophilia. To support these phenotypic results, transcriptional analysis revealed that celastrol down-regulated the expression of biofilm- and virulence- associated genes (smeYZ, fsnR, and bfmAK) in S. maltophilia. Interestingly, celastrol significantly inhibited the expression of smeYZ gene, which encodes the resistance-nodulation-division (RND)-type efflux pump, SmeYZ. Overall, our findings suggested that celastrol might be a promising bioactive agent for treatment of biofilm- and virulence-related infections caused by the multi-drug resistant S. maltophilia.
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spelling pubmed-59304642018-05-03 Anti-biofilm and Anti-Virulence Efficacy of Celastrol Against Stenotrophomonas maltophilia Kim, Hye-Rim Lee, Dongsup Eom, Yong-Bin Int J Med Sci Research Paper Stenotrophomonas maltophilia is a multi-drug resistant opportunistic pathogen that causes nosocomial infections in immunocompromised patients. This pathogen is difficult to treat owing to its intrinsic multidrug resistance and ability to form antimicrobial-tolerant biofilms. In the present study, we aimed to assess the potential use of celastrol as a novel anti-biofilm and/or anti-virulence agent against S. maltophilia. Results showed that celastrol at its sub-inhibitory doses decreased biofilm formation and disrupt the established biofilms produced by S. maltophilia. Celastrol-induced decrease in biofilm formation was dose-dependent based on the results of the microtiter plate biofilm assays and confocal laser scanning microscopy. In addition, our data validated the anti-virulence efficacy of celastrol, wherein it significantly interfered with the production of protease and motility of S. maltophilia. To support these phenotypic results, transcriptional analysis revealed that celastrol down-regulated the expression of biofilm- and virulence- associated genes (smeYZ, fsnR, and bfmAK) in S. maltophilia. Interestingly, celastrol significantly inhibited the expression of smeYZ gene, which encodes the resistance-nodulation-division (RND)-type efflux pump, SmeYZ. Overall, our findings suggested that celastrol might be a promising bioactive agent for treatment of biofilm- and virulence-related infections caused by the multi-drug resistant S. maltophilia. Ivyspring International Publisher 2018-03-28 /pmc/articles/PMC5930464/ /pubmed/29725253 http://dx.doi.org/10.7150/ijms.23924 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Kim, Hye-Rim
Lee, Dongsup
Eom, Yong-Bin
Anti-biofilm and Anti-Virulence Efficacy of Celastrol Against Stenotrophomonas maltophilia
title Anti-biofilm and Anti-Virulence Efficacy of Celastrol Against Stenotrophomonas maltophilia
title_full Anti-biofilm and Anti-Virulence Efficacy of Celastrol Against Stenotrophomonas maltophilia
title_fullStr Anti-biofilm and Anti-Virulence Efficacy of Celastrol Against Stenotrophomonas maltophilia
title_full_unstemmed Anti-biofilm and Anti-Virulence Efficacy of Celastrol Against Stenotrophomonas maltophilia
title_short Anti-biofilm and Anti-Virulence Efficacy of Celastrol Against Stenotrophomonas maltophilia
title_sort anti-biofilm and anti-virulence efficacy of celastrol against stenotrophomonas maltophilia
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930464/
https://www.ncbi.nlm.nih.gov/pubmed/29725253
http://dx.doi.org/10.7150/ijms.23924
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