DiRita V J, Parsot C, Jander G, Mekalanos J J
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5403-7. doi: 10.1073/pnas.88.12.5403.
Expression of more than 17 virulence genes in Vibrio cholerae is under the coordinate control of the ToxR protein. ToxR is a transmembrane protein that binds to and activates the promoter of the operon encoding cholera toxin. As yet, the ability of ToxR to activate directly other genes in this regulon has not been demonstrated. We have cloned a gene called toxT from V. cholerae 569B; the toxT gene product, like ToxR, can activate the ctx promoter in Escherichia coli. In addition, expression of other genes identified as members of the ToxR regulon (tcpA, tcpI, aldA, and tagA) can be activated in E. coli by the toxT gene product but not by ToxR. When expressed from a constitutive promoter, the toxT gene product partially suppresses the ToxR- phenotype of a toxR deletion mutant of V. cholerae. The level of toxT mRNA is greatly reduced in a toxR mutant of V. cholerae. In addition, growth conditions under which the ToxR regulon is not expressed also repress the synthesis of toxT mRNA. These results suggest that ToxR controls transcription of toxT, whose product in turn is directly responsible for activation of several virulence genes under ToxR control.
霍乱弧菌中17种以上毒力基因的表达受ToxR蛋白的协同调控。ToxR是一种跨膜蛋白，它能结合并激活编码霍乱毒素的操纵子的启动子。到目前为止，尚未证明ToxR直接激活该调控子中其他基因的能力。我们从霍乱弧菌569B中克隆了一个名为toxT的基因；toxT基因产物与ToxR一样，能在大肠杆菌中激活ctx启动子。此外，toxT基因产物可在大肠杆菌中激活被鉴定为ToxR调控子成员的其他基因（tcpA、tcpI、aldA和tagA）的表达，但ToxR不能。当从组成型启动子表达时，toxT基因产物可部分抑制霍乱弧菌toxR缺失突变体的ToxR表型。在霍乱弧菌的toxR突变体中，toxT mRNA的水平大幅降低。此外，ToxR调控子不表达的生长条件也会抑制toxT mRNA的合成。这些结果表明，ToxR控制toxT的转录，而toxT的产物反过来直接负责激活ToxR控制下的几个毒力基因。
