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Bacterial persisters: molecular mechanisms and therapeutic development

SIGNAL TRANSDUCTION AND TARGETED THERAPY 2024年第1期9卷 1-32页

作者： Niu, Hongxia Gu, Jiaying Zhang, Ying Zhejiang Chinese Med Univ Sch Basic Med Sci Hangzhou 310053 Zhejiang Peoples R China Zhejiang Chinese Med Univ Key Lab Blood Stasis Toxin Syndrome Zhejiang Prov Hangzhou 310053 Zhejiang Peoples R China Zhejiang Univ Affiliated Hosp 1 Sch Med State Key Lab Diag & Treatment Infect Dis Hangzhou 310003 Zhejiang Peoples R China Jinan Microecol Biomed Shandong Lab Jinan 250022 Shandong Peoples R China

Persisters refer to genetically drug susceptible quiescent (non-growing or slow growing) bacteria that survive in stress environments such as antibiotic exposure, acidic and starvation conditions. These cells can regrow after stress removal and remain susceptible to the same stress. Persisters are underlying the problems of treating chronic and persistent infections and relapse infections after treatment, drug resistance development, and biofilm infections, and pose significant challenges for effective treatments. Understanding the characteristics and the exact mechanisms of persister formation, especially the key molecules that affect the formation and survival of the persisters is critical to more effective treatment of chronic and persistent infections. Currently, genes related to persister formation and survival are being discovered and confirmed, but the mechanisms by which bacteria form persisters are very complex, and there are still many unanswered questions. This article comprehensively summarizes the historical background of bacterial persisters, details their complex characteristics and their relationship with antibiotic tolerant and resistant bacteria, systematically elucidates the interplay between various bacterial biological processes and the formation of persister cells, as well as consolidates the diverse anti-persister compounds and treatments. We hope to provide theoretical background for in-depth research on mechanisms of persisters and suggest new ideas for choosing strategies for more effective treatment of persistent infections.

关键词： SMALL-COLONY VARIANTS TOXIN-ANTITOXIN SYSTEMS UROPATHOGENIC ESCHERICHIA-COLI nonculturable vibrio-cholerae MEDIATE ANTIBIOTIC TOLERANCE STAPHYLOCOCCUS-AUREUS MYCOBACTERIUM-TUBERCULOSIS PSEUDOMONAS-AERUGINOSA STATIONARY-PHASE MULTIDRUG TOLERANCE

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