细菌持留与抗生素表型耐药机制.PDF

Hereditas (Beijing) 2016 年 10 月, 38(10): 859―871 综 述 细菌持留与抗生素表型耐药机制 1 1 1 1,2 崔鹏 ，许涛 ，张文宏 ，张颖 1. 200040 2. 21205 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 Molecular mechanisms of bacterial persistence and phenotypic antibiotic resistance 1 1 1 1,2 Peng Cui , Tao Xu , Wenhong Zhang , Ying Zhang 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, Baltimore21205, USA Abstract: Bacterial persistence refers to a state of reduced metabolic activity that endows a subpopulation of iso- genic 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 infec- tions and biofilm infections become apparent. Much research has been done in recent years to investigate the me- chanisms underlying bacterial persistence and phenotypic antibiotic resistance. The mechanisms of bacterial persis- tence are complex and the following pathways are involved in persister formation: toxin-antitoxin systems, reduced metabolism, energy production, protein and nucleic acid