Department of Biology and Antimicrobial Discovery Center, Northeastern University, Boston, Massachusetts 02115, USA.
Annu Rev Microbiol. 2010;64:357-72. doi: 10.1146/annurev.micro.112408.134306.
Persisters are dormant variants of regular cells that form stochastically in microbial populations and are highly tolerant to antibiotics. High persister (hip) mutants of Pseudomonas aeruginosa are selected in patients with cystic fibrosis. Similarly, hip mutants of Candida albicans are selected in patients with an oral thrush biofilm. These observations suggest that persisters may be the main culprit responsible for the recalcitrance of chronic infectious disease to antimicrobial therapy. Screening knockout libraries has not produced mutants lacking persisters, indicating that dormancy mechanisms are redundant. Toxin/antitoxin (TA) modules are involved in persister formation in Escherichia coli. The SOS response leads to overexpression of the TisB toxin and persister formation. TisB is a membrane-acting peptide that apparently sends cells into dormancy by decreasing the proton motive force and ATP levels. Stress responses may act as general activators of persister formation. Proteins required for maintaining persisters may represent realistic targets for discovery of drugs capable of effectively treating chronic infections.
持久型菌是常规细胞的休眠变体，在微生物群体中随机形成，对抗生素具有高度耐受性。铜绿假单胞菌的高持久型（hip）突变体在囊性纤维化患者中被选择。同样，白色念珠菌的 hip 突变体在患有口腔白色念珠菌生物膜的患者中被选择。这些观察结果表明，持久型菌可能是导致慢性传染病对抗生素治疗产生抗药性的主要罪魁祸首。筛选敲除文库并没有产生缺乏持久型菌的突变体，这表明休眠机制是冗余的。毒素/抗毒素（TA）模块参与了大肠杆菌中持久型菌的形成。SOS 反应导致 TisB 毒素的过度表达和持久型菌的形成。TisB 是一种作用于膜的肽，通过降低质子动力势和 ATP 水平，显然会使细胞进入休眠状态。应激反应可能作为持久型菌形成的一般激活剂。维持持久型菌所需的蛋白质可能代表发现能够有效治疗慢性感染的药物的现实目标。
