Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United States.
Front Cell Infect Microbiol. 2023 May 22;13:1185571. doi: 10.3389/fcimb.2023.1185571. eCollection 2023.
In adapting to the intracellular niche, obligate intracellular bacteria usually undergo a reduction of genome size by eliminating genes not needed for intracellular survival. These losses can include, for example, genes involved in nutrient anabolic pathways or in stress response. Living inside a host cell offers a stable environment where intracellular bacteria can limit their exposure to extracellular effectors of the immune system and modulate or outright inhibit intracellular defense mechanisms. However, highlighting an area of vulnerability, these pathogens are dependent on the host cell for nutrients and are very sensitive to conditions that limit nutrient availability. Persistence is a common response shared by evolutionarily divergent bacteria to survive adverse conditions like nutrient deprivation. Development of persistence usually compromises successful antibiotic therapy of bacterial infections and is associated with chronic infections and long-term sequelae for the patients. During persistence, obligate intracellular pathogens are viable but not growing inside their host cell. They can survive for a long period of time such that, when the inducing stress is removed, reactivation of their growth cycles resumes. Given their reduced coding capacity, intracellular bacteria have adapted different response mechanisms. This review gives an overview of the strategies used by the obligate intracellular bacteria, where known, which, unlike model organisms such as , often lack toxin-antitoxin systems and the stringent response that have been linked to a persister phenotype and amino acid starvation states, respectively.
在适应细胞内小生境时，专性细胞内细菌通常通过消除细胞内生存不需要的基因来缩小基因组大小。这些损失可能包括参与营养合成途径或应激反应的基因。生活在宿主细胞内提供了一个稳定的环境，细胞内细菌可以限制其暴露于免疫系统的细胞外效应物，并调节或完全抑制细胞内防御机制。然而，这些病原体依赖于宿主细胞获取营养，并且对限制营养可用性的条件非常敏感，这凸显了一个脆弱的领域。持久性是进化上不同的细菌为了在营养缺乏等不利条件下生存而共同采取的一种反应。持久性的发展通常会影响细菌感染的成功抗生素治疗，并与慢性感染和患者的长期后果相关。在持久性期间，专性细胞内病原体在其宿主细胞内是有活力但不生长的。它们可以存活很长一段时间，以至于当诱导压力消除时，它们的生长周期重新开始激活。由于其编码能力降低，细胞内细菌已经适应了不同的反应机制。这篇综述概述了专性细胞内细菌所使用的策略，已知的策略与模式生物不同，例如，它们通常缺乏与持久表型和氨基酸饥饿状态分别相关的毒素-抗毒素系统和严格反应。
