School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Wadsworth Center, New York State Department of Health, Albany, New York, USA.
Microbiology (Reading). 2023 May;169(5). doi: 10.1099/mic.0.001330.
The closely related transcription factors MarA, SoxS, Rob and RamA control overlapping stress responses in many enteric bacteria. Furthermore, constitutive expression of such regulators is linked to clinical antibiotic resistance. In this work we have mapped the binding of MarA, SoxS, Rob and RamA across the Typhimurium genome. In parallel, we have monitored changes in transcription start site use resulting from expression of the regulators. Together, these data allow direct and indirect gene regulatory effects to be disentangled. Promoter architecture across the regulon can also be deduced. At a phylogenetic scale, around one third of regulatory targets are conserved in most organisms encoding MarA, SoxS, Rob or RamA. We focused our attention on the control of , which encodes a transcriptional activator responsible for stimulating production of curli fibres during biofilm formation. We show that expression of is particularly sensitive to SoxS that binds upstream to repress transcription. This differs to the situation in , where MarA regulates indirectly.
紧密相关的转录因子 MarA、SoxS、Rob 和 RamA 控制着许多肠杆菌的重叠应激反应。此外，这些调节剂的组成型表达与临床抗生素耐药性有关。在这项工作中，我们已经绘制了 MarA、SoxS、Rob 和 RamA 在 Typhimurium 基因组上的结合图谱。同时，我们监测了由于调节剂表达导致的转录起始位点使用的变化。这些数据可以将直接和间接的基因调控效应区分开来。调控子的启动子结构也可以推断出来。在系统发育尺度上，编码 MarA、SoxS、Rob 或 RamA 的大多数生物体中约有三分之一的调控靶标是保守的。我们将注意力集中在 的控制上，该基因编码一种转录激活因子，负责在生物膜形成过程中刺激卷曲纤维的产生。我们表明， 的表达对 SoxS 特别敏感，SoxS 在上游结合以抑制转录。这与 中的情况不同，MarA 间接调节 。
