Article

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

Oregon State University
Microbiology (Impact Factor: 2.84). 02/2013; DOI: 10.1099/mic.0.064865-0
Source: PubMed

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-coenzyme A (acetyl-CoA) and its non-TCA cycle metabolism. Indeed, both the nqr and TCA cycle mutants increased acetate excretion. A similar correlation between acetate excretion and toxT transcription was observed in the tolC mutant and upon amino acid (NRES) supplementation. Since acetate and its tendency to decrease pH exerted no strong effect on toxT transcription, and since 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.

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