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将抗痉挛药物溴化奥替溴铵重新用于治疗感染

Repurposing Antispasmodic Agent Otilonium Bromide for Treatment of Infections.

作者信息

Zhou Linying, She Pengfei, Tan Fang, Li Shijia, Zeng Xianghai, Chen Lihua, Luo Zhen, Wu Yong

机构信息

Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.

出版信息

Front Microbiol. 2020 Jul 31;11:1720. doi: 10.3389/fmicb.2020.01720. eCollection 2020.

Abstract

Recently, the problem of bacterial resistance has been brought into focus, which makes the development of new antibiotics become a necessity. Compared with traditional development approaches, drug repurposing provides a faster and more effective approach to find new antimicrobial agents. In this study, we found that antispasmodic agent otilonium bromide had strong antibacterial ability and bactericidal activity against , with minimal inhibitory concentrations (MICs) of 4-8 μg/ml, and bacteria could be killed completely after treatment with 2× MIC of otilonium bromide for 5 h. Furthermore, it had a potent effect on eradicating biofilm at concentrations ranging from 16 to 64 μg/ml. At the same time, it had low tendency to develop resistance and possessed limited cytotoxicity. In the methicillin-resistant -infected mouse peritonitis model, it was also effective to cure mice and improve their survival rate. In addition, we observed that otilonium bromide changed the permeability of bacterial membrane and caused membrane damage, and it is probably the antibacterial mechanism of otilonium bromide. Taken together, our results indicated that otilonium bromide could be a new antimicrobial agent to treat infections more safely and efficiently.

摘要

最近,细菌耐药性问题已成为焦点,这使得开发新型抗生素成为必要。与传统的开发方法相比,药物重新利用提供了一种更快、更有效的方法来寻找新的抗菌剂。在本研究中,我们发现解痉剂奥替溴铵对[具体细菌名称缺失]具有较强的抗菌能力和杀菌活性,最低抑菌浓度(MIC)为4-8μg/ml,用2×MIC的奥替溴铵处理5小时后细菌可被完全杀死。此外,它在16至64μg/ml的浓度范围内对生物膜的消除有显著效果。同时,它产生耐药性的倾向较低且细胞毒性有限。在耐甲氧西林[具体细菌名称缺失]感染的小鼠腹膜炎模型中,它对治愈小鼠并提高其存活率也有效。此外,我们观察到奥替溴铵改变了细菌膜的通透性并导致膜损伤,这可能是奥替溴铵的抗菌机制。综上所述,我们的结果表明奥替溴铵可能是一种更安全、有效地治疗[具体细菌名称缺失]感染的新型抗菌剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa17/7410927/44271d11a935/fmicb-11-01720-g001.jpg

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