Jatrorrhizine suppresses the antimicrobial resistance of methicillin‑resistant Staphylococcus aureus

Yu,Haiming; Wang,Yuefei; Wang,Xiaoqing; Guo,Junjie; Wang,Hui; Zhang,Hao; Du,Fengxia

doi:10.3892/etm.2019.8034

Jatrorrhizine suppresses the antimicrobial resistance of methicillin‑resistant Staphylococcus aureus

Authors:
- Haiming Yu
- Yuefei Wang
- Xiaoqing Wang
- Junjie Guo
- Hui Wang
- Hao Zhang
- Fengxia Du
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Affiliations: Department of Cerebral Surgery, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China, Department of Physiology, Physiology Section of Basic Medical Science College, Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China, Central Laboratory, General Hospital of Daqing Oil Field, Daqing, Heilongjiang 163411, P.R. China, Department of Pathogen Biology, Medical Technology College of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China, Department of Immunology, Medical Technology College of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China
Published online on: September 23, 2019 https://doi.org/10.3892/etm.2019.8034
Pages: 3715-3722
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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