Bicarbonate increases binding affinity of Vibrio cholerae ToxT to virulence gene promoters.
Bicarbonate increases binding affinity of Vibrio cholerae ToxT to virulence gene promoters.
复制标题
碳酸氢盐增加霍乱弧菌 ToxT 与毒力基因启动子的结合亲和力。
DOI：
10.1128/jb.01824-14
复制
发表时间：
2014
影响因子：
3.2
通讯作者：
Withey,JeffreyH
中科院分区：
文献类型：
--
作者：
Thomson,JoshuaJ;Withey,JeffreyH
霍乱弧菌主要毒力基因转录激活因子ToxT负责产生霍乱弧菌诱导的霍乱毒素（CT）和主要定植因子毒素共调节菌毛（TCP）。除了上述两个主要毒力因子外，ToxT还负责激活辅助毒力基因，如aldA、tagA、acfA、acfD、tcpI和tarAB。ToxT活性受胆汁和小肠上部发现的不饱和脂肪酸的负调节。相反，以前的工作确定了另一种肠道信号，碳酸氢盐，它增强了ToxT激活CT和TCP产生的能力。本文提出的工作进一步阐明了碳酸氢盐增强ToxT活性的机制。发现Biclidine除了产生CT和TCP的启动子外，还增加了ToxT依赖性辅助毒力启动子的激活。Biclidine被摄入霍乱弧菌细胞，在那里它通过增加对毒力基因启动子的DNA结合亲和力而积极影响ToxT活性，而不管毒盒构型如何，ToxT激活毒力基因启动子。在重碳酸盐存在下ToxT结合亲和力的增加解释了毒力基因转录水平的升高。
The major Vibrio cholerae virulence gene transcription activator, ToxT, is responsible for the production of the diarrhea-inducing cholera toxin (CT) and the major colonization factor, toxin coregulated pilus (TCP). In addition to the two primary virulence factors mentioned, ToxT is responsible for the activation of accessory virulence genes, such asaldA,tagA,acfA,acfD,tcpI, andtarAB. ToxT activity is negatively modulated by bile and unsaturated fatty acids found in the upper small intestine. Conversely, previous work identified another intestinal signal, bicarbonate, which enhances the ability of ToxT to activate production of CT and TCP. The work presented here further elucidates the mechanism for the enhancement of ToxT activity by bicarbonate. Bicarbonate was found to increase the activation of ToxT-dependent accessory virulence promoters in addition to those that produce CT and TCP. Bicarbonate is taken up into the V. cholerae cell, where it positively affects ToxT activity by increasing DNA binding affinity for the virulence gene promoters that ToxT activates regardless of toxbox configuration. The increase in ToxT binding affinity in the presence of bicarbonate explains the elevated level of virulence gene transcription.