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Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant Staphylococcus aureus
Bacterial resistance to antimicrobial agents, including multidrug resistance, is an increasing problem in the treatment of infectious diseases. The development of resistance-modifying agents represents a potential strategy to alleviate the spread of bacterial resistance to antibiotics. A checkerboar...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781805/ https://www.ncbi.nlm.nih.gov/pubmed/31616505 http://dx.doi.org/10.3892/etm.2019.8034 |
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author | Yu, Haiming Wang, Yuefei Wang, Xiaoqing Guo, Junjie Wang, Hui Zhang, Hao Du, Fengxia |
author_facet | Yu, Haiming Wang, Yuefei Wang, Xiaoqing Guo, Junjie Wang, Hui Zhang, Hao Du, Fengxia |
author_sort | Yu, Haiming |
collection | PubMed |
description | Bacterial resistance to antimicrobial agents, including multidrug resistance, is an increasing problem in the treatment of infectious diseases. The development of resistance-modifying agents represents a potential strategy to alleviate the spread of bacterial resistance to antibiotics. A checkerboard microdilution assay was used to determine the synergy of jatrorrhizine and the antibiotic, norfloxacin (NFX). A bacterial ethidium bromide efflux assay, reverse transcription semi-quantitative polymerase chain reaction analysis and molecular docking study were performed. The three-dimensional structure of NorA multidrug efflux pump (NorA) was generated using a multiple threading approach. A murine thigh infection model was used to evaluate the in vivo synergistic effect. As a natural product, jatrorrhizine exhibited little antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) SA1199B with a minimum inhibitory concentration (MIC) of 64 mg/l. According to the investigations of the mechanism, jatrorrhizine significantly inhibited bacterial drug efflux and the expression of NorA in the mRNA level as it can bind to NorA by hydrogen-bonds, hydrophobic and electrostatic interactions. The in vivo synergistical bactericidal activity of jatrorrhizine and NFX against MRSA was confirmed in a murine thigh infection model. As a novel resistance-modifying agent, jatrorrhizine exhibited in vitro and in vivo synergistic activities against MRSA, and inhibited bacterial drug efflux. The effects were mediated by the suppression of NorA mRNA expression and/or interactions with NorA efflux pump. These data support the hypothesis that jatrorrhizine is a potential agent for therapeutic use in infections caused by MRSA. |
format | Online Article Text |
id | pubmed-6781805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-67818052019-10-15 Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant Staphylococcus aureus Yu, Haiming Wang, Yuefei Wang, Xiaoqing Guo, Junjie Wang, Hui Zhang, Hao Du, Fengxia Exp Ther Med Articles Bacterial resistance to antimicrobial agents, including multidrug resistance, is an increasing problem in the treatment of infectious diseases. The development of resistance-modifying agents represents a potential strategy to alleviate the spread of bacterial resistance to antibiotics. A checkerboard microdilution assay was used to determine the synergy of jatrorrhizine and the antibiotic, norfloxacin (NFX). A bacterial ethidium bromide efflux assay, reverse transcription semi-quantitative polymerase chain reaction analysis and molecular docking study were performed. The three-dimensional structure of NorA multidrug efflux pump (NorA) was generated using a multiple threading approach. A murine thigh infection model was used to evaluate the in vivo synergistic effect. As a natural product, jatrorrhizine exhibited little antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) SA1199B with a minimum inhibitory concentration (MIC) of 64 mg/l. According to the investigations of the mechanism, jatrorrhizine significantly inhibited bacterial drug efflux and the expression of NorA in the mRNA level as it can bind to NorA by hydrogen-bonds, hydrophobic and electrostatic interactions. The in vivo synergistical bactericidal activity of jatrorrhizine and NFX against MRSA was confirmed in a murine thigh infection model. As a novel resistance-modifying agent, jatrorrhizine exhibited in vitro and in vivo synergistic activities against MRSA, and inhibited bacterial drug efflux. The effects were mediated by the suppression of NorA mRNA expression and/or interactions with NorA efflux pump. These data support the hypothesis that jatrorrhizine is a potential agent for therapeutic use in infections caused by MRSA. D.A. Spandidos 2019-11 2019-09-23 /pmc/articles/PMC6781805/ /pubmed/31616505 http://dx.doi.org/10.3892/etm.2019.8034 Text en Copyright: © Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Yu, Haiming Wang, Yuefei Wang, Xiaoqing Guo, Junjie Wang, Hui Zhang, Hao Du, Fengxia Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant Staphylococcus aureus |
title | Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant Staphylococcus aureus |
title_full | Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant Staphylococcus aureus |
title_fullStr | Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant Staphylococcus aureus |
title_full_unstemmed | Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant Staphylococcus aureus |
title_short | Jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant Staphylococcus aureus |
title_sort | jatrorrhizine suppresses the antimicrobial resistance of methicillin-resistant staphylococcus aureus |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781805/ https://www.ncbi.nlm.nih.gov/pubmed/31616505 http://dx.doi.org/10.3892/etm.2019.8034 |
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