Bacterial persistence - Bacterial persistence is an active σS stress response to metabolic flux limitation

Bacterial persistence, found in dormant and starved cells, is a health threat due to transient antibiotic tolerance. Harnessing a novel method for persister generation, we determined the proteome, metabolite levels and the physiology of E.coli persisters in and during entry into dormancy and starvation. In contrast to starved persisters, dormant persisters present in nutrient-rich conditions produced energy and grew, while both types had extremely low metabolite pools. The proteome of dormant cells governed by starvation response reached a unique state characterized by diminished anabolism, stress response and preservation of central metabolism protein levels. While starved cells approaches the same proteome, the limited carbon and energy source did not allow them to reach it, which caused their higher sensitivity to certain antibiotics. We present a conceptual model in which depleted metabolite pools resulting from initial persistence triggers provide a primitive, feed-forward starvation signal that sustains the growing persistent phenotype.

细菌持留性（bacterial persistence）存在于休眠与饥饿细胞中，可通过瞬时抗生素耐受特性对人类健康构成威胁。本研究借助一种全新的持留菌构建方法，系统解析了大肠杆菌（E.coli）在进入休眠与饥饿状态过程中以及处于该状态下的蛋白质组（proteome）、代谢物水平与生理特征。与饥饿状态下的持留菌不同，在营养富足环境中存活的休眠持留菌可产生能量并进行增殖，而两类持留菌的代谢物池均处于极低水平。受饥饿应答调控的休眠细胞蛋白质组呈现出独特状态，具体表现为合成代谢减弱、应激应答受到调控且中枢代谢相关蛋白水平得以维持。尽管饥饿状态的细胞也趋近于该蛋白质组状态，但有限的碳源与能源供给使其无法达到这一状态，进而导致其对特定抗生素的敏感性显著升高。本研究提出了一套概念模型：初始持留触发过程中耗尽的代谢物池，可形成一种原始的前馈式饥饿信号，从而维持增殖型持留表型。