The type VI nanomachine is critical for Vibrio cholerae to establish infections and to thrive in niches co‐occupied by competing bacteria. The genes for the type VI structural proteins are encoded in one large and two small auxiliary gene clusters. VCA0117 (VasH) – a σ⁵⁴‐transcriptional activator – is strictly required for functionality of the type VI secretion system since it controls production of the structural protein Hcp. While some strains constitutively produce a functional system, others do not and require specific growth conditions of low temperature and high osmolarity for expression of the type VI machinery. Here, we trace integration of these regulatory signals to the promoter activity of the large gene cluster in which many components of the machinery and VCA0117 itself are encoded. Using in vivo and in vitro assays and variants of VCA0117, we show that activation of the σ⁵⁴‐promoters of the auxiliary gene clusters by elevated VCA0117 levels are all that is required to overcome the need for specialized growth conditions. We propose a model in which signal integration via the large operon promoter directs otherwise restrictive levels of VCA0117 that ultimately dictates a sufficient supply of Hcp for completion of a functional type VI secretion system.

中文翻译：

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响应外部信号，VCA0117（VasH）水平升高会激活霍乱弧菌O1 El Tor A1552的VI型分泌系统。

VI型纳米机器对于霍乱弧菌建立感染并在竞争细菌共同占据的生态位中壮成长至关重要。VI型结构蛋白的基​​因编码在一个大和两个小辅助基因簇中。VCA0117（VASH） -一个σ ⁵⁴转录激活剂– VI型分泌系统功能的严格要求，因为它控制结构蛋白Hcp的产生。虽然某些菌株组成性地产生功能系统，但其他菌株则不需要，并且需要低温和高渗透压的特定生长条件才能表达VI型机械。在这里，我们跟踪这些调节信号的整合到大型基因簇的启动子活性中，其中许多机械元件和VCA0117本身都被编码。使用体内和体外测定法和VCA0117的变体中，我们表明了σ的活化⁵⁴通过提高VCA0117水平来辅助基因簇的启动子是克服特殊生长条件所需的全部。我们提出了一个模型，在该模型中，通过大操纵子启动子的信号整合将指导VCA0117的限制性水平，而该水平最终指示为完成功能性VI分泌系统提供充足的Hcp。