(p)ppGpp, a small nucleotide regulator, directs the metabolic fate of glucose in Vibrio cholerae [Metabolism]

April 16th, 2015 by Oh, Y. T., Lee, K.-M., Bari, W., Raskin, D. M., Yoon, S. S.

When V. cholerae encounters nutritional stress, it activates (p)ppGpp-mediated stringent response (SR). The genes, relA and relV, are involved in the production of (p)ppGpp, while the spoT gene encodes an enzyme that hydrolyzes it. Herein, we show that the bacterial capability to produce (p)ppGpp plays an essential role in glucose metabolism. The V. cholerae mutants defective in (p)ppGpp production (i.e., ∆relA∆relV and ∆relA∆relV∆spoT mutants) lost their viability due to uncontrolled production of organic acids, when grown with extra glucose. In contrast, the ∆relA∆spoT mutant, a (p)ppGpp overproducer strain, exhibited better growth in the presence of the same glucose concentration. An RNA sequencing analysis demonstrated that transcriptions of genes, consisting of an operon for acetoin biosynthesis were markedly elevated in N16961, a 7th pandemic O1 strain, but not in its (p)ppGpp0 mutant during glucose-stimulated growth. Transposon insertion in acetoin biosynthesis gene cluster resulted in glucose-induced loss of viability of the ∆relA∆spoT mutant, further suggesting the crucial role of acetoin production in balanced growth under glucose-rich environments. Additional deletion of the aphA gene, encoding a negative regulator for acetoin production, failed to rescue the (p)ppGpp0 mutant from the defective glucose-mediated growth, suggesting that (p)ppGpp-mediated acetoin production occurs independent of the presence of AphA. Overall, our results reveal that (p)ppGpp, in addition to its well-known role as a SR mediator, positively regulates acetoin production that contributes to the successful glucose metabolism and consequently the proliferation of V. cholerae cells under a glucose-rich environment, a condition that may mimic the human intestine.