Department of Chemistry, Chair of Biochemistry, Technische Universität München, Garching, Germany.
Chair of Microbiology, Biocenter, University of Würzburg, Würzburg, Germany.
Front Cell Infect Microbiol. 2021 Jan 14;10:615450. doi: 10.3389/fcimb.2020.615450. eCollection 2020.
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.
持久性已进化为一种强大的生存策略，以克服不利的环境条件。这种能力几乎存在于所有细菌中，包括所有人类细菌病原体，并且可能与这些病原体中的一些引起的慢性感染有关。尽管大多数细菌细胞群体将被特定的应激源（如抗生素、氧和氮自由基、营养饥饿等）杀死，但一个不同的亚群（称为持久菌）将能够承受应激情况，并在应激消除后恢复活力。过去已经确定了几个有利于持久性形成的因素和途径，例如各种毒素/抗毒素模块或严格反应以及警报素（p）ppGpp。然而，即使在无应激的细菌群体中，少数细胞也可能会随机发生持久性。这些细胞的生长随后可以被应激条件诱导。在这篇综述中，我们专注于人类细胞内细菌病原体的持久菌形成，其中一些属于最成功的持久菌产生菌，但缺乏一些甚至所有假设的持久性触发因素和途径。我们提出了一种这些细菌病原体形成持久菌的机制，该机制基于它们特定的细胞内二分体代谢。我们假设，这种代谢方式最终会导致 DNA 复制起始的停滞，这可能是持久菌状态的原因。
