title: Central metabolism controls transcription of a virulence gene regulator in Vibrio cholerae.
abstract: ToxT is the central regulatory protein involved in activation of the main virulence genes in Vibrio cholerae. We have identified transposon insertions in central metabolism genes, whose disruption increases toxT transcription. These disrupted genes encode the primary respiration-linked sodium pump (NADH:ubiquinone oxidoreductase or NQR) and certain tricarboxylic acid (TCA) cycle enzymes. Observations made following stimulation of respiration in the nqr mutant or chemical inhibition of NQR activity in the TCA cycle mutants led to the hypothesis that NQR affects toxT transcription via the TCA cycle. That toxT transcription increased when the growth medium was supplemented with citrate, but decreased with oxaloacetate, focused our attention on the TCA cycle substrate acetyl-CoA and its non-TCA cycle metabolism. Indeed, both the nqr and the TCA cycle mutants increased acetate excretion. A similar correlation between acetate excretion and toxT transcription was observed in a tolC mutant and upon amino acid (NRES) supplementation. As acetate and its tendency to decrease pH exerted no strong effect on toxT transcription, and because disruption of the major acetate excretion pathway increased toxT transcription, we propose that toxT transcription is regulated by either acetyl-CoA or some close derivative.
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors: Yusuke
authors: Y
authors: Minato
authors: Department of Microbiology, College of Science, Oregon State University, Corvallis, OR, USA.
authors: Sara R
authors: SR
authors: Fassio
authors: Department of Microbiology and Immunology, Health Sciences Division, Loyola University Chicago, Maywood, IL, USA.
authors: Alan J
authors: AJ
authors: Wolfe
authors: Department of Microbiology, College of Science, Oregon State University, Corvallis, OR, USA.|Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors: Claudia C
authors: CC
authors: Häse
mesh_terms: D000085:Acetates / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism* / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019343:Citric Acid / Q000378:metabolism; D002952:Citric Acid Cycle / Q000235:genetics / Q000502:physiology; D003470:Culture Media / Q000737:chemistry; D004251:DNA Transposable Elements; D015964:Gene Expression Regulation, Bacterial; D016254:Mutagenesis, Insertional; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D041241:Vibrio cholerae O1 / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D000085:Acetates; D000596:Amino Acids; D001426:Bacterial Proteins; D003470:Culture Media; D004251:DNA Transposable Elements; D014157:Transcription Factors; C075626:tcpN protein, Vibrio cholerae; D019343:Citric Acid; D000105:Acetyl Coenzyme A