细菌持留与抗生素表型耐药机制

doi:10.16288/j.yczz.16-213

遗传 ›› 2016, Vol. 38 ›› Issue (10): 859-871.doi: 10.16288/j.yczz.16-213

细菌持留与抗生素表型耐药机制

崔鹏¹, 许涛¹, 张文宏¹, 张颖^{1, 2}

1. 复旦大学附属华山医院感染科,上海 200040;
2. 约翰·霍普金斯大学布隆伯格公共卫生学院,巴尔的摩 21205

收稿日期:2016-06-15 修回日期:2016-07-11 出版日期:2016-10-20 发布日期:2016-10-20
作者简介:张颖,博士,教授,研究方向：细菌耐药。
基金资助:
国家自然科学基金项目(编号：81101226, 81471987)资助

Molecular mechanisms of bacterial persistence and phenotypic antibiotic resistance

Peng Cui¹, Tao Xu¹, Wenhong Zhang¹, Ying Zhang^{1, 2}

1. Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China;
2. Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore 21205, USA

Received:2016-06-15 Revised:2016-07-11 Online:2016-10-20 Published:2016-10-20
Supported by:
[Supported by the National Natural Science Foundation of China; (Nos; 81101226, 81471987)]

摘要/Abstract

摘要： 持留菌是细菌群体中一小部分具有表型耐药的细菌。自1944年被发现后,近几十年来因其在慢性持续性感染和生物膜感染中的重要作用而得到越来越多的重视。已有的研究结果表明,细菌持留的机理复杂,涉及的相关信号通路有毒素-抗毒素系统、细胞能量代谢及蛋白核酸合成等生理状态的降低、DNA保护修复系统、蛋白酶系统、反式翻译、外排泵系统等。虽然不同细菌的持留机理有一定的相似性和保守性,但不同细菌的持留机制也存在差异,如毒素-抗毒素系统在大肠埃希菌(Escherichia coli)中的过度激活可导致持留菌增加,但在金黄色葡萄球菌(Staphylococcus aureus)中却并无相同作用。本文从持留菌的研究历史出发,综述了当前对革兰氏阴性菌和阳性菌的持留机制方面的研究进展,同时探讨了在持留菌相关感染疾病方面的治疗策略,以期为更好地解决持留菌带来的问题,缩短治疗时间提供新的思路。

关键词: 抗生素, 持留菌, 大肠埃希菌, 金黄色葡萄球菌, 代谢, 毒素-抗毒素系统

Abstract: Bacterial persistence refers to a state of reduced metabolic activity that endows a subpopulation of isogenic bacteria with multidrug tolerance. Persisters are phenotypic variants but not mutants. Since its discovery in 1944, bacterial persistence has not received enough attention until recently when its implications in persistent infections and biofilm infections become apparent. Much research has been done in recent years to investigate the mechanisms underlying bacterial persistence and phenotypic antibiotic resistance. The mechanisms of bacterial persistence are complex and the following pathways are involved in persister formation: toxin-antitoxin systems, reduced metabolism, energy production, protein and nucleic acid synthesis, DNA repair and protection, protein degradation, transporters/efflux systems, and transcriptional regulators etc. Although persistence mechanisms are conserved in terms of the gene function and pathways involved among different bacterial species, they may vary in gene homology and relative importance of a given pathway. For example, Escherichia coli toxin-antitoxin systems play an important role in persister formation, while Staphylococcus aureus persister formation does not appear to use toxin-antitoxin systems. Here we provide an update on recent progress in persistence mechanisms using E. coli and S. aureus as models, as well as discuss approaches in the treatment of persistent bacterial infections.

Key words: antibiotics, persisters, E. coli, S. aureus, metabolism, TA system

崔鹏, 许涛, 张文宏, 张颖. 细菌持留与抗生素表型耐药机制[J]. 遗传, 2016, 38(10): 859-871.

Peng Cui, Tao Xu, Wenhong Zhang, Ying Zhang. Molecular mechanisms of bacterial persistence and phenotypic antibiotic resistance[J]. Hereditas(Beijing), 2016, 38(10): 859-871.

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细菌持留与抗生素表型耐药机制

Molecular mechanisms of bacterial persistence and phenotypic antibiotic resistance

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