The modified nucleotides (p)ppGpp play an important role in bacterial physiology. While the accumulation of the nucleotides is vital for adaptation to various kinds of stress, changes in the basal level modulates growth rate and vice versa. Studying the phenotypes unique to the strain lacking (p)ppGpp (ppGpp 0 ) under overtly unstressed growth conditions may be useful to understand functions regulated by basal levels of (p)ppGpp and its physiological significance. In this study, we show that the ppGpp 0 strain, unlike the wild type, requires the Lon protease for cell division and viability in LB. Our results indicate the decrease in FtsZ concentration in the ppGpp 0 strain makes cell division vulnerable to SulA inhibition. We did not find evidence for SOS induction contributing to the cell division defect in the ppGpp 0 ⌬lon strain. Based on the results, we propose that basal levels of (p)ppGpp are required to sustain normal cell division in Escherichia coli during growth in rich medium and that the basal SulA level set by Lon protease is important for insulating cell division against a decrease in FtsZ concentration and conditions that can increase the susceptibility of FtsZ to SulA.
IMPORTANCEThe physiology of the stringent response has been the subject of investigation for more than 4 decades, with the majority of the work carried out using the bacterial model organism Escherichia coli. These studies have revealed that the accumulation of (p)ppGpp, the effector of the stringent response, is associated with growth retardation and changes in gene expression that vary with the intracellular concentration of (p)ppGpp. By studying a synthetic lethal phenotype, we have uncovered a function modulated by the basal levels of (p)ppGpp and studied its physiological significance. Our results show that (p)ppGpp and Lon protease contribute to the robustness of the cell division machinery in E. coli during growth in rich medium.A daptation in response to stress is a universal trait among living organisms. In eubacteria and plants, two modified nucleotides, namely, guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), collectively referred to as (p)ppGpp, have been implicated in adaptation to various nutritional and environmental stresses (1-5). By far the best-studied stress response mediated by (p)ppGpp is the stringent response in the bacterial model organism Escherichia coli, and it is characterized by the repression of rRNA transcription and the activation of amino acid biosynthetic genes. This adaptation requires the RelA-mediated synthesis of (p)ppGpp in response to amino acid starvation and results in the extensive reprogramming of gene expression globally (6, 7). More commonly, the stringent response also refers to responses caused by elevating (p)ppGpp by other means. In E. coli, relA and spoT genes are involved in (p)ppGpp metabolism and are part of the RSH (Rel-Spo homolog) superfamily of genes conserved in eubacteria and plants (3,8). (p)ppGpp is synthesized in response to amino acid st...