Repression of Escherichia coli PhoP-PhoQ signaling by acetate reveals a regulatory role for acetyl coenzyme A.
The PhoP-PhoQ two-component system regulates the transcription of numerous genes in response to changes in extracellular divalent cation concentration and pH. Here we demonstrate that the Escherichia coli PhoP-PhoQ two-component system also responds to acetate. Signaling by the E. coli PhoP-PhoQ system was repressed during growth in acetate (> or = 25 mM) in a PhoQ-dependent manner. The periplasmic sensor domain of PhoQ was not required for acetate to repress signaling. Acetate-mediated repression of the PhoP-PhoQ system was not related to changes in the intracellular concentration of acetate metabolites such as acetyl-phosphate or acetyladenylate. Genetic analysis of acetate metabolism pathways suggested that a perturbation of acetyl coenzyme A turnover was the cause of decreased PhoP-PhoQ signaling during growth in acetate. Consistent with this hypothesis, intracellular acetyl coenzyme A levels rose during growth in the presence of exogenous acetate. Acetyl coenzyme A inhibited the autokinase activity of PhoQ in vitro, suggesting that the in vivo repressing effect may be due to a direct inhibition mechanism.
Lesley
Joseph A
JA
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Waldburger
Carey D
CD
D000085:Acetates / Q000494:pharmacology; D000105:Acetyl Coenzyme A / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D003470:Culture Media; D015536:Down-Regulation; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D000071677:Histidine Kinase; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000085:Acetates; D001426:Bacterial Proteins; D003470:Culture Media; D029968:Escherichia coli Proteins; C465562:PhoP protein, E coli; C079792:PhoQ protein, Bacteria; D047428:Protein Kinase Inhibitors; D000105:Acetyl Coenzyme A; D011494:Protein Kinases; D000071677:Histidine Kinase