title: Pyruvate-associated acid resistance in bacteria.
abstract: Glucose confers acid resistance on exponentially growing bacteria by repressing formation of the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex and consequently activating acid resistance genes. Therefore, in a glucose-rich growth environment, bacteria are capable of resisting acidic stresses due to low levels of cAMP-CRP. Here we reveal a second mechanism for glucose-conferred acid resistance. We show that glucose induces acid resistance in exponentially growing bacteria through pyruvate, the glycolysis product. Pyruvate and/or the downstream metabolites induce expression of the small noncoding RNA (sncRNA) Spot42, and the sncRNA, in turn, activates expression of the master regulator of acid resistance, RpoS. In contrast to glucose, pyruvate has little effect on levels of the cAMP-CRP complex and does not require the complex for its effects on acid resistance. Another important difference between glucose and pyruvate is that pyruvate can be produced by bacteria. This means that bacteria have the potential to protect themselves from acidic stresses by controlling glucose-derived generation of pyruvate, pyruvate-acetate efflux, or reversion from acetate to pyruvate. We tested this possibility by shutting down pyruvate-acetate efflux and found that the resulting accumulation of pyruvate elevated acid resistance. Many sugars can be broken into glucose, and the subsequent glycolysis generates pyruvate. Therefore, pyruvate-associated acid resistance is not confined to glucose-grown bacteria but is functional in bacteria grown on various sugars.
authors.affiliation: Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, China.
authors.forename: Jianting
authors.initials: J
authors.lastname: Wu
authors.affiliation: Center for Synthetic Biology Engineering Research, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Shenzhen University Town, Shenzhen, China.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, China Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China yejin@cuhk.edu.hk caizhiming2000@163.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Medicine and Therapeutics and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, NT, Hong Kong yejin@cuhk.edu.hk caizhiming2000@163.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Jin
mesh_terms: D003001:Cloning, Molecular; D002373:Cyclic AMP Receptor Protein / Q000378:metabolism; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D019289:Pyruvic Acid / Q000378:metabolism*; D058727:RNA, Small Untranslated / Q000235:genetics* / Q000378:metabolism
chemical_list: D002373:Cyclic AMP Receptor Protein; D058727:RNA, Small Untranslated; D019289:Pyruvic Acid; D005947:Glucose