In addition to the well-known strategies of antibiotic resistance and biofilm formation, bacterial populations possess an additional survival strategy to endure hostile environments or antibiotic exposure. A small fraction of transiently antibiotic-tolerant phenotypical variants, called persister cells, is capable of surviving treatment with high doses of antibiotics. When antibiotic pressure drops, persisters that switch back to a normal phenotype can resume growth, ensuring survival of the bacterial population. Persister cells have been identified in every major pathogen, contribute to the antibiotic tolerance observed in biofilms, and are responsible for the recalcitrant nature of chronic infections. Also, evidence is accumulating that persister cells can contribute to the emergence of antibiotic resistance. Consequently, effective treatment of persister cells could greatly improve patient outcome. The small number of persisters and the redundancy in mechanisms of persister formation impede target-based development of anti-persister therapies. Nonetheless, the armory of anti-persister molecules is increasing. This review presents a comprehensive overview of anti-persister molecules and strategies described in literature to date and offers perspectives on potential anti-persistence targets and methods for the development of future therapies. Furthermore, we highlight in vivo model systems for pre-clinical testing and summarize ongoing clinical trials of candidate anti-persister therapeutics.

除了众所周知的抗生素抗性和生物膜形成策略外，细菌种群还具有另一种生存策略，可以承受恶劣的环境或抗生素暴露。称为持久性细胞的一小部分瞬时耐受抗生素的表型变异体能够在高剂量抗生素的情况下存活下来。当抗生素压力下降时，切换回正常表型的持久性物质可以恢复生长，从而确保细菌种群的生存。在每种主要病原体中均已鉴定出持久性细胞，其有助于生物膜中观察到的抗生素耐受性，并导致慢性感染的顽固性。同样，越来越多的证据表明，持久性细胞可以促进抗生素耐药性的出现。所以，有效治疗持久性细胞可大大改善患者预后。持久性的数量少和持久性形成机制的冗余性阻碍了基于目标的抗持久疗法的发展。但是，反持久分子的武器库正在增加。这篇综述提供了迄今为止文献中描述的抗持久分子和策略的全面概述，并提供了有关潜在抗持久目标和未来疗法开发方法的观点。此外，我们强调 这篇综述提供了迄今为止文献中描述的抗持久分子和策略的全面概述，并提供了有关潜在抗持久目标和未来疗法开发方法的观点。此外，我们强调 这篇综述提供了迄今为止文献中描述的抗持久分子和策略的全面概述，并提供了有关潜在抗持久目标和未来疗法开发方法的观点。此外，我们强调用于临床前测试的体内模型系统，并总结了正在进行的候选抗persister疗法的临床试验。