Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei Province, China.
Nat Commun. 2023 Jan 28;14(1):467. doi: 10.1038/s41467-023-36254-0.
Timely adaptation to nutrient downshift is crucial for bacteria to maintain fitness during feast and famine cycle in the natural niche. However, the molecular mechanism that ensures the timely adaption of bacterial growth to nutrient downshift remains poorly understood. Here, we quantitatively investigated the adaptation of Escherichia coli to various kinds of nutrient downshift. We found that relA deficient strain, which is devoid of stringent response, exhibits a significantly longer growth lag than wild type strain during adapting to both amino acid downshift and carbon downshift. Quantitative proteomics show that increased (p)ppGpp level promotes the growth adaption of bacteria to amino acid downshift via triggering the proteome resource re-allocation from ribosome synthesis to amino acid biosynthesis. Such type of proteome re-allocation is significantly delayed in the relA-deficient strain, which underlies its longer lag than wild type strain during amino acid downshift. During carbon downshift, a lack of stringent response in relA deficient strain leads to disruption of the transcription-translation coordination, thus compromising the transcription processivity and further the timely expression of related catabolic operons for utilizing secondary carbon sources. Our studies shed light on the fundamental strategy of bacteria to maintain fitness under nutrient-fluctuating environments.
及时适应营养物质的减少对于细菌在自然环境中的丰俭周期中保持适应性至关重要。然而，确保细菌生长及时适应营养物质减少的分子机制仍知之甚少。在这里，我们定量研究了大肠杆菌对各种营养物质减少的适应。我们发现，缺乏严格反应的 relA 缺陷菌株在适应氨基酸减少和碳源减少时，比野生型菌株表现出明显更长的生长滞后。定量蛋白质组学表明，增加的（p）ppGpp 水平通过触发核糖体合成到氨基酸生物合成的蛋白质组资源重新分配，促进了细菌对氨基酸减少的生长适应。这种蛋白质组的重新分配在 relA 缺陷菌株中明显延迟，这导致其在氨基酸减少时比野生型菌株具有更长的滞后时间。在碳源减少时，relA 缺陷菌株缺乏严格反应会导致转录-翻译协调的破坏，从而影响转录过程的连续性，并进一步影响利用次级碳源的相关分解代谢操纵子的及时表达。我们的研究揭示了细菌在营养物质波动环境中保持适应性的基本策略。
