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首页> 外文期刊>Molecular Microbiology >Multiple factors contribute to bimodal toxin gene expression in Clostridioides Clostridioides ( Clostridium) difficile Clostridium) difficile
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Multiple factors contribute to bimodal toxin gene expression in Clostridioides Clostridioides ( Clostridium) difficile Clostridium) difficile

机译：多种因素有助于蛋白质梭菌梭菌（Clostridium）艰难梭菌梭菌的双峰毒素基因表达）艰难岩

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Summary Clostridioides (formerly Clostridium ) difficile produces two major toxins, TcdA and TcdB, upon entry into stationary phase. Transcription of tcdA and tcdB requires the specialized sigma factor, σ TcdR , which also directs RNA Polymerase to transcribe tcdR itself. We fused a gene for a red fluorescent protein to the tcdA promoter to study toxin gene expression at the level of individual C. difficile cells. Surprisingly, only a subset of cells became red fluorescent upon entry into stationary phase. Breaking the positive feedback loop that controls σ TcdR production by engineering cells to express tcdR from a tetracycline‐inducible promoter resulted in uniform fluorescence across the population. Experiments with two regulators of tcdR expression, σ D and CodY, revealed neither is required for bimodal toxin gene expression. However, σ D biased cells toward the Toxin‐ON state, while CodY biased cells toward the Toxin‐OFF state. Finally, toxin gene expression was observed in sporulating cells. We conclude that (i) toxin production is regulated by a bistable switch governed by σ TcdR , which only accumulates to high enough levels to trigger toxin gene expression in a subset of cells, and (ii) toxin production and sporulation are not mutually exclusive developmental programs.
机译：发明内容梭菌（以前的梭菌）艰难梭菌在进入固定阶段时产生两个主要毒素，TCDA和TCDB。 TCDA和TCDB的转录需要专门的Sigma因子，σTCDR，其也引导RNA聚合酶转录TCDR本身。我们融合了一种用于TCDA启动子的红色荧光蛋白的基因，以研究毒素基因表达在单个C.艰难梭菌细胞的水平。令人惊讶的是，在进入固定阶段时，只有一个细胞的子集变为红色荧光。破坏通过工程细胞控制ΣTCDR产生的正反馈环，以表达来自四环素诱导的启动子的TCDR导致整个群体的均匀荧光。具有两种TCDR表达，σd和Cody的调节剂的实验既不需要双峰毒素基因表达所需的。然而，σd偏向细胞朝向毒素导通状态，而Cody偏向细胞朝向毒素关闭状态。最后，在孢子化细胞中观察到毒素基因表达。我们得出结论，（i）毒素生产由σTCDR治理的双稳态开关调节，该开关仅累积足够高的水平以引发细胞子集中的毒素基因表达，并且（ii）毒素的生产和孢子产物不是相互排斥的发展程式。

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  • 来源
    《Molecular Microbiology》 |2018年第4期|共17页
  • 作者

    Ransom Eric M.; Kaus Gabriela M.; Tran Phuong M.; Ellermeier Craig D.; Weiss David S.;

  • 作者单位

    Department of Microbiology and ImmunologyCarver College of Medicine University of IowaIowa City IA;

    Department of Microbiology and ImmunologyCarver College of Medicine University of IowaIowa City IA;

    Department of Microbiology and ImmunologyCarver College of Medicine University of IowaIowa City IA;

    Department of Microbiology and ImmunologyCarver College of Medicine University of IowaIowa City IA;

    Department of Microbiology and ImmunologyCarver College of Medicine University of IowaIowa City IA;

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  • 正文语种 eng
  • 中图分类 细胞生物学;
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