细菌固有耐药的研究进展.pdfVIP

Hereditas (Beijing) 2016 年 10 月, 38(10): 872 ―880 综 述 细菌固有耐药的研究进展 张刚，冯婕 中国科学院微生物研究所，微生物资源前期开发国家重点实验室，北京 100101 摘要 : 人们以往大多只关注由敏感细菌通过基因水平转移和自发突变方式获得的耐药性，而忽略了细菌对某类 抗生素天然耐药的重要特性，细菌的这种特性又被称为固有耐药。固有耐药由固有耐药基因决定，这类基因是 指存在于某类细菌染色体上位置保守的与耐药相关的一类基因。近年来，对固有耐药基因的研究已经越来越受 到重视。固有耐药基因的发现不仅可以为新药研制提供药物作用靶标，而且通过阻断病原菌固有耐药基因还可 使以往对该类菌不起作用的抗生素药物重新焕发抗菌活性。此外，已有研究表明固有耐药基因能够被移动元件 捕获进而可水平转移至其他细菌，因此通过监测固有耐药基因可以预测耐药菌的出现。本文对传统的细菌固有 耐药机制包括细胞膜的低渗透性和多药外排泵系统，以及已知重要病原菌的转移酶和代谢相关酶的固有耐药机 制进行了介绍。同时，进一步对隐性固有耐药基因的特性进行了阐释，最后探讨了固有耐药与获得性耐药的进 化关系，指出固有耐药基因很可能是一些获得性耐药基因的来源。 关键词 : 固有耐药；隐性耐药基因；外排泵；修饰酶；水解酶 The intrinsic resistance of bacteria Gang Zhang, Jie Feng State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China Abstract : Antibiotic resistance is often considered to be a trait acquired by previously susceptible bacteria, on the basis of which can be attributed to the horizontal acquisition of new genes or the occurrence of spontaneous mu- tation. In addition to acquired resistance, bacteria have a trait of intrinsic resistance to different classes of antibiotics. An intrinsic resistance gene is involved in intrinsic resistance, and its presence in bacterial strains is independent of previous antibiotic exposure and is not caused by horizontal gene transfer. Recently, interest in intrinsic resistance genes has increased, because these gene products not only may provide attractive therapeutic targets for development of novel drugs that rejuvenate the activity of existing antibiotics, and but also might predict future emergence of re- sistant pathogens if they become mobilized. In the present review, we summarize the conventional examples of in- trinsic resistance, including the impermeability of cellular envelopes, the activity of multidrug efflux pumps or lack of dr