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肠杆菌科细菌喹诺酮耐药相关的分子机制:综述与更新

Molecular mechanisms associated with quinolone resistance in Enterobacteriaceae: review and update.

作者信息

Azargun Robab, Gholizadeh Pourya, Sadeghi Vahid, Hosainzadegan Hasan, Tarhriz Vahideh, Memar Mohammad Yousef, Pormohammad Ali, Eyvazi Shirin

机构信息

Department of Microbiology, Faculty of Medicine, Maragheh University of Medical Sciences, Maragheh, Iran.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Trans R Soc Trop Med Hyg. 2020 Oct 5;114(10):770-781. doi: 10.1093/trstmh/traa041.

Abstract

BACKGROUND

Quinolones are broad-spectrum antibiotics, which are used for the treatment of different infectious diseases associated with Enterobacteriaceae. During recent decades, the wide use as well as overuse of quinolones against diverse infections has led to the emergence of quinolone-resistant bacterial strains. Herein, we present the development of quinolone antibiotics, their function and also the different quinolone resistance mechanisms in Enterobacteriaceae by reviewing recent literature.

METHODS

All data were extracted from Google Scholar search engine and PubMed site, using keywords; quinolone resistance, Enterobacteriaceae, plasmid-mediated quinolone resistance, etc.

RESULTS AND CONCLUSION

The acquisition of resistance to quinolones is a complex and multifactorial process. The main resistance mechanisms consist of one or a combination of target-site gene mutations altering the drug-binding affinity of target enzymes. Other mechanisms of quinolone resistance are overexpression of AcrAB-tolC multidrug-resistant efflux pumps and downexpression of porins as well as plasmid-encoded resistance proteins including Qnr protection proteins, aminoglycoside acetyltransferase (AAC(6')-Ib-cr) and plasmid-encoded active efflux pumps such as OqxAB and QepA. The elucidation of resistance mechanisms will help researchers to explore new drugs against the resistant strains.

摘要

背景

喹诺酮类是广谱抗生素,用于治疗与肠杆菌科相关的不同传染病。在最近几十年中,喹诺酮类药物广泛用于以及过度用于治疗各种感染,导致了喹诺酮耐药菌株的出现。在此,我们通过回顾近期文献,介绍喹诺酮类抗生素的发展、其功能以及肠杆菌科中不同的喹诺酮耐药机制。

方法

所有数据均从谷歌学术搜索引擎和PubMed网站提取,使用的关键词有:喹诺酮耐药性、肠杆菌科、质粒介导的喹诺酮耐药性等。

结果与结论

获得对喹诺酮类药物的耐药性是一个复杂且多因素的过程。主要耐药机制包括一个或多个改变靶酶药物结合亲和力的靶位点基因突变。喹诺酮耐药的其他机制包括AcrAB - tolC多药耐药外排泵过表达、孔蛋白下调以及质粒编码的耐药蛋白,包括Qnr保护蛋白、氨基糖苷乙酰转移酶(AAC(6') - Ib - cr)和质粒编码的主动外排泵,如OqxAB和QepA。对耐药机制的阐明将有助于研究人员探索针对耐药菌株的新药。

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