Persistence has evolved as a potent survival strategy to overcome adverse environmental conditions. This capability is common to almost all bacteria, including all human bacterial pathogens and likely connected to chronic infections caused by some of these pathogens. Although the majority of a bacterial cell population will be killed by the particular stressors, like antibiotics, oxygen and nitrogen radicals, nutrient starvation and others, a varying subpopulation (termed persisters) will withstand the stress situation and will be able to revive once the stress is removed. Several factors and pathways have been identified in the past that apparently favor the formation of persistence, such as various toxin/antitoxin modules or stringent response together with the alarmone (p)ppGpp. However, persistence can occur stochastically in few cells even of stress-free bacterial populations. Growth of these cells could then be induced by the stress conditions. In this review, we focus on the persister formation of human intracellular bacterial pathogens, some of which belong to the most successful persister producers but lack some or even all of the assumed persistence-triggering factors and pathways. We propose a mechanism for the persister formation of these bacterial pathogens which is based on their specific intracellular bipartite metabolism. We postulate that this mode of metabolism ultimately leads, under certain starvation conditions, to the stalling of DNA replication initiation which may be causative for the persister state.

持久性已发展成为克服不利环境条件的有效生存策略。几乎所有细菌（包括所有人类细菌病原体）都具有这种功能，并且可能与其中某些病原体引起的慢性感染有关。尽管大多数细菌细胞群会被特定的应激源杀死，例如抗生素，氧自由基和氮自由基，营养缺乏等，但不同的亚群（称为持久性）将承受压力的状况，并且一旦压力恢复原样已移除。过去已经发现了一些显然有助于持久性形成的因素和途径，例如各种毒素/抗毒素模块或与警戒（p）ppGpp一起的严格应答。然而，即使在没有压力的细菌群体中，持久性也可能在少数细胞中随机发生。这些细胞的生长然后可以由应激条件诱导。在这篇综述中，我们集中于人类细胞内细菌病原体的持久性形成，其中一些病原体是最成功的持久性生产者，但缺乏某些甚至所有假定的持久性触发因素和途径。我们提出了一种机制，这些细菌病原体的持久性形成基于其特定的细胞内二分代谢。我们假设这种新陈代谢模式最终会在某些饥饿条件下导致DNA复制起始的停止，这可能是持久状态的原因。在这篇综述中，我们集中于人类细胞内细菌病原体的持久性形成，其中一些病原体是最成功的持久性生产者，但缺乏某些甚至所有假定的持久性触发因素和途径。我们提出了一种机制，这些细菌病原体的持久性形成基于其特定的细胞内二分代谢。我们假设这种新陈代谢模式最终会在某些饥饿条件下导致DNA复制起始的停止，这可能是持久状态的原因。在这篇综述中，我们集中于人类细胞内细菌病原体的持久性形成，其中一些病原体是最成功的持久性生产者，但缺乏某些甚至所有假定的持久性触发因素和途径。我们提出了一种机制，这些细菌病原体的持久性形成基于其特定的细胞内二分代谢。我们假设这种新陈代谢模式最终会在某些饥饿条件下导致DNA复制起始的停止，这可能是持久状态的原因。我们提出了一种机制，这些细菌病原体的持久性形成基于其特定的细胞内二分代谢。我们假设这种新陈代谢模式最终会在某些饥饿条件下导致DNA复制起始的停止，这可能是持久状态的原因。我们提出了一种机制，这些细菌病原体的持久性形成基于其特定的细胞内二分代谢。我们假设这种新陈代谢模式最终会在某些饥饿条件下导致DNA复制起始的停止，这可能是持久状态的原因。