Central metabolism controls transcription of a virulence gene regulator in Vibrio cholerae
Central metabolism controls transcription of a virulence gene regulator in Vibrio cholerae
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DOI：
10.1099/mic.0.064865-0
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发表时间：
2013-04-01
期刊：
影响因子：
2.8
通讯作者：
Haese, Claudia C.
中科院分区：
文献类型：
--
作者：
Minato, Yusuke;Fassio, Sara R.;Haese, Claudia C.
ToxT是参与霍乱弧菌主要毒力基因激活的中心调节蛋白。我们已经确定了转座子插入中央代谢基因，其中断增加toxT转录。这些被破坏的基因编码初级呼吸相关钠泵（NADH：泛醌氧化还原酶或NOR）和某些三羧酸（TCA）循环酶。在nqr突变体中刺激呼吸或在TCA循环突变体中化学抑制NOR活性后进行的观察导致NOR通过TCA循环影响toxT转录的假设。当生长培养基中补充柠檬酸盐时，toxT转录增加，但草酰乙酸降低，将我们的注意力集中在TCA循环底物乙酰辅酶A及其非TCA循环代谢上。事实上，nqr和TCA循环突变体都增加了乙酸盐的排泄。在to/C突变体和氨基酸（NRES）补充剂中观察到乙酸排泄和toxT转录之间的类似相关性。由于乙酸盐及其降低pH的趋势对toxT转录没有强烈的影响，并且由于主要乙酸盐排泄途径的破坏增加了toxT转录，因此我们提出toxT转录受乙酰辅酶A或一些接近的衍生物的调节。
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 NOR) and certain tricarboxylic acid (TCA) cycle enzymes. Observations made following stimulation of respiration in the nqr mutant or chemical inhibition of NOR activity in the TCA cycle mutants led to the hypothesis that NOR 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 to/C 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.