1887

Abstract

ToxT is the central regulatory protein involved in activation of the main virulence genes in . We have identified transposon insertions in central metabolism genes, whose disruption increases 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 mutant or chemical inhibition of NQR activity in the TCA cycle mutants led to the hypothesis that NQR affects transcription via the TCA cycle. That 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 and the TCA cycle mutants increased acetate excretion. A similar correlation between acetate excretion and transcription was observed in a mutant and upon amino acid (NRES) supplementation. As acetate and its tendency to decrease pH exerted no strong effect on transcription, and because disruption of the major acetate excretion pathway increased transcription, we propose that transcription is regulated by either acetyl-CoA or some close derivative.

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2013-04-01
2020-11-30
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