REGULATORY CASCADE CONTROLS VIRULENCE IN VIBRIO-CHOLERAE
REGULATORY CASCADE CONTROLS VIRULENCE IN VIBRIO-CHOLERAE
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DOI：
10.1073/pnas.88.12.5403
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发表时间：
1991-06-01
影响因子：
11.1
通讯作者：
MEKALANOS, JJ
中科院分区：
文献类型：
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作者：
DIRITA, VJ;PARSOT, C;MEKALANOS, JJ
霍乱弧菌中17种毒力基因的表达受ToxR蛋白的协调调控。ToxR是一种跨膜蛋白，结合并激活编码霍乱毒素的操纵子的启动子。到目前为止，ToxR直接激活该调节子中的其他基因的能力还没有被证明。我们已经从霍乱弧菌569B中克隆了一个名为toxT的基因，该基因产物和ToxR一样，可以激活大肠杆菌中的CTX启动子。此外，被鉴定为ToxR调节子成员的其他基因(TCPA、TCPI、ALDA和TagA)的表达可以在ToxT基因产物中被激活，但不能被ToxR激活。当从构成启动子表达时，toxT基因产物部分抑制霍乱弧菌toxR缺失突变体的ToxR表型。霍乱弧菌toxR突变株的toxT基因表达水平显著降低。此外，不表达ToxR调节子的生长条件也抑制了ToxT mRNA的合成。这些结果表明，ToxR控制ToxT的转录，而ToxT的产物直接激活了ToxR控制下的几个毒力基因。
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 bv 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.