title: Decoding genome-wide GadEWX-transcriptional regulatory networks reveals multifaceted cellular responses to acid stress in Escherichia coli.
abstract: 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.
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Seo
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Donghyuk
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: O'Brien
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Szubin
authors.affiliation: 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.|Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Lyngby, Denmark.
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Palsson
mesh_terms: D051777:AraC Transcription Factor / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D016680:Genome, Bacterial; D006863:Hydrogen-Ion Concentration; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051777:AraC Transcription Factor; D029968:Escherichia coli Proteins; C479562:GadE protein, E coli; C474648:GadW protein, E coli; C446316:GadX protein, E coli; D014157:Transcription Factors