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Fluidity is an inherent property of biological membranes and its maintenance (homeoviscous adaptation) is important for optimal functioning of membrane‐associated processes. The fluidity of bacterial cytoplasmic membrane increases with temperature or an increase in the proportion of unsaturated fatty acids and vice versa. We found that strains deficient in the synthesis of guanine nucleotide analogs (p)ppGpp and lacking FadR, a transcription factor involved in fatty acid metabolism exhibited a growth defect that was rescued by an increase in growth temperature or unsaturated fatty acid content. The strain lacking (p)ppGpp was sensitive to genetic or chemical perturbations that decrease the proportion of unsaturated fatty acids over saturated fatty acids. Microscopy showed that the growth defect was associated with cell filamentation and lysis and rescued by combined expression of cell division genes ftsQ, ftsA, and ftsZ from plasmid or the gain‐of‐function ftsA* allele but not over‐expression of ftsN. The results implicate (p)ppGpp in positive regulation of cell division during membrane fluidity loss through enhancement of FtsZ proto‐ring stability. To our knowledge, this is the first report of a (p)ppGpp‐mediated regulation needed for adaptation to membrane fluidity loss in bacteria. [ABSTRACT FROM AUTHOR]

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 (ppGpp0) 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 ppGpp0 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 ppGpp0 strain makes cell division vulnerable to SulA inhibition. We did not find evidence for SOS induction contributing to the cell division defect in the ppGpp0 ∆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. [ABSTRACT FROM AUTHOR]

Small molecules generally activate or inhibit gene transcription as externally added substrates or as internally accumulated end- products, respectively. Rarely has a connection been made that links an intracellular intermediary metabolite as a signal of gene expression. We report that a perturbation in the critical step of a metabolic pathway-the D-galactose amphibolic pathway- changes the dynamics of the pathways leading to accumulation of the intermediary metabolite UDP-galactose. This accumulation causes cell stress and transduces signals that alter gene expression so as to cope with the stress by restoring balance in the metabolite pool. This underscores the importance of studying the global effects of alterations in the level of intermediary metabolites in causing stress and coping with it by transducing signals to genes to reach a stable state of equilibrium (homeostasis). Such studies are an essential component in the integration of metabolomics, proteomics, and transcriptomics. [ABSTRACT FROM AUTHOR]