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Polymyxin B in Combination with Glycerol Monolaurate Exerts Synergistic Killing against Gram-Negative Pathogens

The rapid emergence and spread of multidrug-resistant (MDR) bacterial pathogens pose a serious danger to worldwide human health, and resistance to last-resort drugs, such as polymyxins, is being increasingly detected in MDR Gram-negative pathogens. There is an urgent need to find and optimize combin...

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Autores principales: Zheng, Yun, Yang, Ning, Ding, Yuting, Li, Jiajia, Liu, Yanyan, Chen, Haoran, Li, Jiabin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413120/
https://www.ncbi.nlm.nih.gov/pubmed/36014995
http://dx.doi.org/10.3390/pathogens11080874
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author Zheng, Yun
Yang, Ning
Ding, Yuting
Li, Jiajia
Liu, Yanyan
Chen, Haoran
Li, Jiabin
author_facet Zheng, Yun
Yang, Ning
Ding, Yuting
Li, Jiajia
Liu, Yanyan
Chen, Haoran
Li, Jiabin
author_sort Zheng, Yun
collection PubMed
description The rapid emergence and spread of multidrug-resistant (MDR) bacterial pathogens pose a serious danger to worldwide human health, and resistance to last-resort drugs, such as polymyxins, is being increasingly detected in MDR Gram-negative pathogens. There is an urgent need to find and optimize combination therapies as an alternative therapeutic strategy, with a dry pipeline in novel antibiotic research and development. We found a monoester formed from the combination of lauric acid and glycerol, glycerol monolaurate (GML), possessing prominent antibacterial and anti-inflammatory activity. However, it is still unclear whether GML in combination could increase antimicrobial activity. Here, we reported that polymyxin B (PMNB) combined with GML exhibited a synergistic antimicrobial impact on Gram-negative strains in vitro, including clinical MDR isolates. This synergistic antimicrobial activity correlated with the destruction of bacterial cell structures, eradication of preformed biofilms, and increased reactive oxygen species (ROS) accumulation. We also showed that PMNB synergized with GML effectively eliminated pathogens from bacterial pneumonia caused by Klebsiella pneumoniae to rescue mice. Our research demonstrated that the PMNB and GML combination induced synergistic antimicrobial activity for Gram-negative pathogens in vitro and in vivo. These findings are of great importance for treating bacterial infections and managing the spread of infectious diseases.
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spelling pubmed-94131202022-08-27 Polymyxin B in Combination with Glycerol Monolaurate Exerts Synergistic Killing against Gram-Negative Pathogens Zheng, Yun Yang, Ning Ding, Yuting Li, Jiajia Liu, Yanyan Chen, Haoran Li, Jiabin Pathogens Article The rapid emergence and spread of multidrug-resistant (MDR) bacterial pathogens pose a serious danger to worldwide human health, and resistance to last-resort drugs, such as polymyxins, is being increasingly detected in MDR Gram-negative pathogens. There is an urgent need to find and optimize combination therapies as an alternative therapeutic strategy, with a dry pipeline in novel antibiotic research and development. We found a monoester formed from the combination of lauric acid and glycerol, glycerol monolaurate (GML), possessing prominent antibacterial and anti-inflammatory activity. However, it is still unclear whether GML in combination could increase antimicrobial activity. Here, we reported that polymyxin B (PMNB) combined with GML exhibited a synergistic antimicrobial impact on Gram-negative strains in vitro, including clinical MDR isolates. This synergistic antimicrobial activity correlated with the destruction of bacterial cell structures, eradication of preformed biofilms, and increased reactive oxygen species (ROS) accumulation. We also showed that PMNB synergized with GML effectively eliminated pathogens from bacterial pneumonia caused by Klebsiella pneumoniae to rescue mice. Our research demonstrated that the PMNB and GML combination induced synergistic antimicrobial activity for Gram-negative pathogens in vitro and in vivo. These findings are of great importance for treating bacterial infections and managing the spread of infectious diseases. MDPI 2022-08-02 /pmc/articles/PMC9413120/ /pubmed/36014995 http://dx.doi.org/10.3390/pathogens11080874 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zheng, Yun
Yang, Ning
Ding, Yuting
Li, Jiajia
Liu, Yanyan
Chen, Haoran
Li, Jiabin
Polymyxin B in Combination with Glycerol Monolaurate Exerts Synergistic Killing against Gram-Negative Pathogens
title Polymyxin B in Combination with Glycerol Monolaurate Exerts Synergistic Killing against Gram-Negative Pathogens
title_full Polymyxin B in Combination with Glycerol Monolaurate Exerts Synergistic Killing against Gram-Negative Pathogens
title_fullStr Polymyxin B in Combination with Glycerol Monolaurate Exerts Synergistic Killing against Gram-Negative Pathogens
title_full_unstemmed Polymyxin B in Combination with Glycerol Monolaurate Exerts Synergistic Killing against Gram-Negative Pathogens
title_short Polymyxin B in Combination with Glycerol Monolaurate Exerts Synergistic Killing against Gram-Negative Pathogens
title_sort polymyxin b in combination with glycerol monolaurate exerts synergistic killing against gram-negative pathogens
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413120/
https://www.ncbi.nlm.nih.gov/pubmed/36014995
http://dx.doi.org/10.3390/pathogens11080874
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