School of Immunity and Infection School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
Mol Microbiol. 2011 Jul;81(1):179-91. doi: 10.1111/j.1365-2958.2011.07685.x. Epub 2011 May 18.
Enteroaggregative Escherichia coli (EAEC) is a major cause of diarrhoea in developing countries. EAEC 042 is the prototypical strain. EAEC 042 secretes the functionally well-characterized Pet autotransporter toxin that contributes to virulence through its cytotoxic effects on intestinal epithelial cells. Following a global transposon mutagenesis screen of EAEC 042, the transcription factors, CRP and Fis, were identified as essential for transcription of the pet gene. Using both in vivo and in vitro techniques, we show that the pet promoter is co-dependent on CRP and Fis. We present a novel co-activation mechanism whereby CRP is placed at a non-optimal position for transcription initiation, creating dependence on Fis for full activation of pet. This study complements previous findings that establish Fis as a key virulence regulator in EAEC 042.
肠聚集性大肠杆菌（EAEC）是发展中国家腹泻的主要病因。EAEC 042 是典型的菌株。EAEC 042 分泌功能良好的 Pet 自动转运毒素，通过对肠上皮细胞的细胞毒性作用促进其毒力。对 EAEC 042 进行全基因组转座子突变筛选后，鉴定出转录因子 CRP 和 Fis 是 pet 基因转录所必需的。我们使用体内和体外技术表明，Pet 启动子依赖于 CRP 和 Fis 共同调控。我们提出了一个新的协同激活机制，即 CRP 被置于转录起始的非最佳位置，因此依赖于 Fis 才能充分激活 pet。这项研究补充了先前的发现，即 Fis 是 EAEC 042 中关键的毒力调节因子。
