Stringent response ensures the timely adaptation of bacterial growth to nutrient downshift

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.