Seo Sang Woo, Kim Donghyuk, O'Brien Edward J, Szubin Richard, Palsson Bernhard O
Department of Bioengineering, University of California San Diego, La Jolla, California 92093, USA.
Department of Pediatrics, University of California San Diego, La Jolla, California 92093, USA.
Nat Commun. 2015 Aug 10;6:7970. doi: 10.1038/ncomms8970.
The regulators GadE, GadW and GadX (which we refer to as GadEWX) play a critical role in the transcriptional regulation of the glutamate-dependent acid resistance (GDAR) system in Escherichia coli K-12 MG1655. However, the genome-wide regulatory role of GadEWX is still unknown. Here we comprehensively reconstruct the genome-wide GadEWX transcriptional regulatory network and RpoS involvement in E. coli K-12 MG1655 under acidic stress. Integrative data analysis reveals that GadEWX regulons consist of 45 genes in 31 transcription units and 28 of these genes were associated with RpoS-binding sites. We demonstrate that GadEWX directly and coherently regulate several proton-generating/consuming enzymes with pairs of negative-feedback loops for pH homeostasis. In addition, GadEWX regulate genes with assorted functions, including molecular chaperones, acid resistance, stress response and other regulatory activities. These results show how GadEWX simultaneously coordinate many cellular processes to produce the overall response of E. coli to acid stress.
调控因子GadE、GadW和GadX（我们将其称为GadEWX）在大肠杆菌K-12 MG1655中依赖谷氨酸的酸抗性（GDAR）系统的转录调控中发挥着关键作用。然而，GadEWX在全基因组范围内的调控作用仍不清楚。在此，我们全面重建了酸性应激条件下大肠杆菌K-12 MG1655中全基因组的GadEWX转录调控网络以及RpoS的参与情况。综合数据分析表明，GadEWX调控子由31个转录单元中的45个基因组成，其中28个基因与RpoS结合位点相关。我们证明，GadEWX通过成对的负反馈环直接且协调地调控几种质子生成/消耗酶，以维持pH稳态。此外，GadEWX调控具有多种功能的基因，包括分子伴侣、酸抗性、应激反应和其他调控活动。这些结果展示了GadEWX如何同时协调许多细胞过程，以产生大肠杆菌对酸应激的整体反应。
