Department of Microbial Pathogenesis, Yale School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore.
Sci Signal. 2021 Jan 26;14(667):eabc4235. doi: 10.1126/scisignal.abc4235.
When cells run out of nutrients, the growth rate greatly decreases. Here, we report that microorganisms, such as the bacterium serovar Typhimurium, speed up the return to a rapid growth state by preventing the proteolysis of functional proteins by ATP-dependent proteases while in the slow-growth state or stationary phase. This reduction in functional protein degradation resulted from a decrease in the intracellular concentration of ATP that was nonetheless sufficient to allow the continued degradation of nonfunctional proteins by the same proteases. Protein preservation occurred under limiting magnesium, carbon, or nitrogen conditions, indicating that this response was not specific to low availability of a particular nutrient. Nevertheless, the return to rapid growth required proteins that mediate responses to the specific nutrient limitation conditions, because the transcriptional regulator PhoP was necessary for rapid recovery only after magnesium starvation. Reductions in intracellular ATP and in ATP-dependent proteolysis also enabled the yeast to recover faster from stationary phase. Our findings suggest that protein preservation during a slow-growth state is a conserved microbial strategy that facilitates the return to a growth state once nutrients become available.
当细胞耗尽营养物质时，其生长速度会大大降低。在这里，我们报告称，微生物（如沙门氏菌血清型鼠伤寒）通过在缓慢生长状态或静止期阻止 ATP 依赖性蛋白酶对功能性蛋白质的蛋白水解作用，从而加速恢复快速生长状态。这种功能性蛋白质降解的减少是由于细胞内 ATP 浓度降低所致，但这足以允许相同的蛋白酶继续降解非功能性蛋白质。在限制镁、碳或氮的条件下发生蛋白质保存，表明这种反应不是特定于特定营养物质的低可用性。然而，要恢复快速生长，需要介导对特定营养限制条件的反应的蛋白质，因为只有在镁饥饿后，转录调节因子 PhoP 才是快速恢复所必需的。细胞内 ATP 的减少和 ATP 依赖性蛋白酶的减少也使酵母能够更快地从静止期恢复。我们的研究结果表明，在缓慢生长状态下保存蛋白质是一种保守的微生物策略，有助于在营养物质可用时恢复生长状态。
