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(p)ppGpp, a Small Nucleotide Regulator, Directs the Metabolic Fate of Glucose in Vibrio cholerae

 Young Taek Oh  ;  Kang-Mu Lee  ;  Wasimul Bari  ;  David M. Raskin  ;  Sang Sun Yoon 
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.290(21) : 13178-13190, 2015 
Journal Title
Issue Date
Acetoin/metabolism* ; Acids/metabolism ; Cell Survival ; Fermentation ; Gene Expression Regulation, Bacterial/drug effects* ; Glucose/metabolism* ; Guanosine Pentaphosphate/pharmacology* ; High-Throughput Nucleotide Sequencing ; Humans ; Ligases/genetics ; Ligases/metabolism* ; Mutation/genetics ; RNA, Bacterial/genetics ; Vibrio cholerae/genetics ; Vibrio cholerae/growth & development* ; Vibrio cholerae/metabolism*
(p)ppGpp ; Vibrio cholerae ; acetoin fermentation ; bacterial metabolism ; bacterial pathogenesis ; carbohydrate metabolism ; stress response ; stringent response
When V. cholerae encounters nutritional stress, it activates (p)ppGpp-mediated stringent response. The genes relA and relV are involved in the production of (p)ppGpp, whereas 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. ΔrelAΔrelV and ΔrelAΔrelVΔspoT mutants) lost their viability because of uncontrolled production of organic acids, when grown with extra glucose. In contrast, the ΔrelAΔspoT 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 seventh pandemic O1 strain, but not in its (p)ppGpp(0) mutant during glucose-stimulated growth. Transposon insertion in acetoin biosynthesis gene cluster resulted in glucose-induced loss of viability of the ΔrelAΔspoT 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)ppGpp(0) 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 stringent response 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.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Sang Sun(윤상선) ORCID logo https://orcid.org/0000-0003-2979-365X
Lee, Kang Mu(이강무) ORCID logo https://orcid.org/0000-0001-7414-5921
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