Institute of Molecular Biosciences, University of Graz, Humboldtstraße 50, Graz, A-8010, Austria.
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, 19104-6076, USA.
Mol Microbiol. 2018 Dec;110(5):796-810. doi: 10.1111/mmi.14125. Epub 2018 Oct 25.
In Vibrio cholerae, virulence gene expression is regulated by a transmembrane-localized transcription factor complex designated as ToxRS. ToxR harbours two cysteines in the periplasmic domain that can form inter- and intramolecular disulfide bonds. In this study, we investigated the σ -dependent inner membrane proteolysis of ToxR, which occurs via the periplasmic-localized proteases DegS and DegP. Both proteases respond to the redox state of the two cysteine thiol groups of ToxR. Interestingly, in the presence of sodium deoxycholate, ToxR proteolysis is blocked independently of ToxS, whereas ToxR activation by bile salts requires ToxS function. From these data, we identified at least two levels of control for ToxR activation by sodiumdeoxycholate. First, bile inhibits ToxR degradation under starvation and alkaline pH or under conditions in which DegPS responds to the reduced disulfide bonds of ToxR. The second level links bile to ToxRS complex formation and further activation of its transcription factor activity. Overall, our data suggest a comprehensive bile sensory function for the ToxRS complex during host colonization.
在霍乱弧菌中，毒力基因的表达受到一种跨膜定位的转录因子复合物的调节，该复合物被指定为 ToxRS。ToxR 在其周质域中含有两个半胱氨酸，这些半胱氨酸可以形成分子间和分子内二硫键。在本研究中，我们研究了 ToxR 的σ 依赖性内膜蛋白酶解，该过程通过周质定位的蛋白酶 DegS 和 DegP 发生。这两种蛋白酶都响应 ToxR 两个半胱氨酸巯基的氧化还原状态。有趣的是，在存在脱氧胆酸钠的情况下，ToxR 蛋白酶解独立于 ToxS 发生，而胆汁盐对 ToxR 的激活需要 ToxS 功能。根据这些数据，我们确定了至少有两个水平的控制来激活 ToxR 对脱氧胆酸钠的反应。首先，胆汁盐在饥饿和碱性 pH 条件下或 DegPS 响应 ToxR 的还原二硫键的条件下抑制 ToxR 的降解。第二个水平将胆汁盐与 ToxRS 复合物的形成以及进一步激活其转录因子活性联系起来。总的来说，我们的数据表明，在宿主定植期间，ToxRS 复合物具有全面的胆汁感应功能。
