Central metabolism controls transcription of a virulence gene regulator in Vibrio cholerae.

TitleCentral metabolism controls transcription of a virulence gene regulator in Vibrio cholerae.
Publication TypeJournal Article
Year of Publication2013
AuthorsMinato Y, Fassio SR, Wolfe AJ, Häse CC
JournalMicrobiology (Reading, England)
Volume159
IssuePt 4
Pagination792-802
Date Published2013 Apr
ISSN1465-2080
KeywordsAcetates, Acetyl Coenzyme A, Amino Acids, Bacterial Proteins, Citric Acid, Citric Acid Cycle, Culture Media, DNA Transposable Elements, Gene Expression Regulation, Bacterial, Mutagenesis, Insertional, Oxygen Consumption, Transcription Factors, Vibrio cholerae O1, Virulence
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.

DOI10.1099/mic.0.064865-0
Alternate JournalMicrobiology (Reading, Engl.)