Coordinated regulation of acid resistance in Escherichia coli

BackgroundEnteric Escherichia coli survives the highly acidic environment of the stomach through multiple acid resistance (AR) mechanisms. The most effective system, AR2, decarboxylates externally-derived glutamate to remove cytoplasmic protons and excrete GABA. The first described system, AR1, does not require an external amino acid. Its mechanism has not been determined. The regulation of the multiple AR systems and their coordination with broader cellular metabolism has not been fully explored.ResultsWe utilized a combination of ChIP-Seq and gene expression analysis to experimentally map the regulatory interactions of four TFs: nac, ntrC, ompR, and csiR. Our data identified all previously in vivo confirmed direct interactions and revealed several others previously inferred from gene expression data. Our data demonstrate that nac and csiR directly modulate AR, and leads to a regulatory network model in which all four TFs participate in coordinating acid resistance, glutamate metabolism, and nitrogen metabolism. This model predicts a novel mechanism for AR1 by which the decarboxylation enzymes of AR2 are used with internally derived glutamate. This hypothesis makes several testable predictions that we confirmed experimentally.ConclusionsOur data suggest that the regulatory network underlying AR is complex and deeply interconnected with the regulation of GABA and glutamate metabolism, nitrogen metabolism. These connections underlie and experimentally validated model of AR1 in which the decarboxylation enzymes of AR2 are used with internally derived glutamate.

• Publication year

  2017

• Venue

  BMC Systems Biology

• Publication date

  2017-01-06

• Fields of study

  Biology, Medicine, Computer Science, Environmental Science

• Identifiers
  DOI 10.1186/s12918-016-0376-yPMID 28061857PMCID 5217608
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Role of intragenic binding of cAMP responsive protein (CRP) in regulation of the succinate dehydrogenase genes Rv0249c-Rv0247c in TB complex mycobacteria

  2015cited by this paper
• The DNA-binding network of Mycobacterium tuberculosis

  2015cited by this paper
• Characterization of a cAMP responsive transcription factor, Cmr (Rv1675c), in TB complex mycobacteria reveals overlap with the DosR (DevR) dormancy regulon

  2015cited by this paper
• Genome-wide Reconstruction of OxyR and SoxRS Transcriptional Regulatory Networks under Oxidative Stress in Escherichia coli K-12 MG1655.

  2015cited by this paper
• Decoding genome-wide GadEWX-transcriptional regulatory networks reveals multifaceted cellular responses to acid stress in Escherichia coli

  2015cited by this paper
• Impact of Anaerobiosis on Expression of the Iron-Responsive Fur and RyhB Regulons

  2015cited by this paper
• The architecture of ArgR-DNA complexes at the genome-scale in Escherichia coli

  2015cited by this paper
• The Influence of Repressor DNA Binding Site Architecture on Transcriptional Control

  2014cited by this paper
• Comprehensive Mapping of the Escherichia coli Flagellar Regulatory Network

  2014cited by this paper
• Nitrogen stress response and stringent response are coupled in Escherichia coli

  2014cited by this paper
• Transcription Factor Binding Site Mapping Using ChIP-Seq

  2014cited by this paper
• Bacterial Regulon Evolution: Distinct Responses and Roles for the Identical OmpR Proteins of Salmonella Typhimurium and Escherichia coli in the Acid Stress Response

  2014influential reference
• Decoding ChIP-seq with a double-binding signal refines binding peaks to single-nucleotides and predicts cooperative interaction

  2014cited by this paper
• Identification of HilD-Regulated Genes in Salmonella enterica Serovar Typhimurium

  2013cited by this paper
• Mechanisms of acid resistance in Escherichia coli.

  2013cited by this paper
• RcsB determines the locus of enterocyte effacement (LEE) expression and adherence phenotype of Escherichia coli O157 : H7 spinach outbreak strain TW14359 and coordinates bicarbonate-dependent LEE activation with repression of motility.

  2013cited by this paper
• Software for Computing and Annotating Genomic Ranges

  2013cited by this paper
• The Mycobacterium tuberculosis regulatory network and hypoxia

  2013cited by this paper
• L-glutamine provides acid resistance for Escherichia coli through enzymatic release of ammonia

  2013cited by this paper
• ChIP-Seq and the complexity of bacterial transcriptional regulation.

  2013cited by this paper
• Genome-scale Analysis of Escherichia coli FNR Reveals Complex Features of Transcription Factor Binding

  2013cited by this paper
• Genome-Scale Analyses of Escherichia coli and Salmonella enterica AraC Reveal Noncanonical Targets and an Expanded Core Regulon

  2013cited by this paper
• Sigma Factor N, Liaison to an ntrC and rpoS Dependent Regulatory Pathway Controlling Acid Resistance and the LEE in Enterohemorrhagic Escherichia coli

  2012cited by this paper
• Fast gapped-read alignment with Bowtie 2

  2012cited by this paper
• EcoCyc: fusing model organism databases with systems biology

  2012influential reference
• Genomic analysis of DNA binding and gene regulation by homologous nucleoid-associated proteins IHF and HU in Escherichia coli K12

  2011cited by this paper
• A systems biology approach sheds new light on Escherichia coli acid resistance

  2011cited by this paper
• A NAC for Regulating Metabolism: the Nitrogen Assimilation Control Protein (NAC) from Klebsiella pneumoniae

  2010cited by this paper
• Direct and indirect effects of H-NS and Fis on global gene expression control in Escherichia coli

  2010cited by this paper
• Acid stress response in Escherichia coli: mechanism of regulation of gadA transcription by RcsB and GadE

  2010cited by this paper
• Inactivation of alternative sigma factor 54 (RpoN) leads to increased acid resistance, and alters locus of enterocyte effacement (LEE) expression in Escherichia coli O157 : H7.

  2010cited by this paper
• A 750 bp sensory integration region directs global control of the Escherichia coli GadE acid resistance regulator

  2009cited by this paper
• A blind deconvolution approach to high-resolution mapping of transcription factor binding sites from ChIP-seq data

  2009cited by this paper
• MEME Suite: tools for motif discovery and searching

  2009cited by this paper
• Prevalence of transcription promoters within archaeal operons and coding sequences

  2009cited by this paper
• The Sequence Alignment/Map format and SAMtools

  2009cited by this paper
• The Escherichia coli AraC-family regulators GadX and GadW activate gadE, the central activator of glutamate-dependent acid resistance.

  2007cited by this paper
• Genome-wide maps of chromatin state in pluripotent and lineage-committed cells

  2007cited by this paper
• Oxygen limitation modulates pH regulation of catabolism and hydrogenases, multidrug transporters, and envelope composition in Escherichia coli K-12

  2006cited by this paper
• CadC-Mediated Activation of the cadBA Promoter in Escherichia coli

  2006cited by this paper
• Transcription Regulation of ompF and ompC by a Single Transcription Factor, OmpR*

  2006cited by this paper
• pH Regulates Genes for Flagellar Motility, Catabolism, and Oxidative Stress in Escherichia coli K-12

  2005cited by this paper
• Functional Characterization in Vitro of All Two-component Signal Transduction Systems from Escherichia coli*

  2005cited by this paper
• Escherichia coli Glutamate- and Arginine-Dependent Acid Resistance Systems Increase Internal pH and Reverse Transmembrane Potential

  2004cited by this paper
• GadE (YhiE): a novel activator involved in the response to acid environment in Escherichia coli.

  2004cited by this paper
• Escherichia coli acid resistance: tales of an amateur acidophile

  2004cited by this paper
• Acid Resistance Systems Required for Survival of Escherichia coli O157:H7 in the Bovine Gastrointestinal Tract and in Apple Cider Are Different

  2004cited by this paper
• Characterization of EvgAS-YdeO-GadE Branched Regulatory Circuit Governing Glutamate-Dependent Acid Resistance in Escherichia coli

  2004cited by this paper
• Regulatory network of acid resistance genes in Escherichia coli

  2003cited by this paper
• Acid resistance in Escherichia coli.

  2003cited by this paper
• GadE (YhiE) activates glutamate decarboxylase‐dependent acid resistance in Escherichia coli K‐12

  2003cited by this paper
• Transcriptional Expression of Escherichia coli Glutamate-Dependent Acid Resistance Genes gadA and gadBC in an hns rpoS Mutant

  2003cited by this paper
• Functional determinants of transcription factors in Escherichia coli: protein families and binding sites.

  2003cited by this paper
• Multiple stress signal integration in the regulation of the complex σS‐dependent csiD‐ygaF‐gabDTP operon in Escherichia coli

  2003influential reference
• Interaction of EnvZ, a sensory histidine kinase, with phosphorylated OmpR, the cognate response regulator

  2002cited by this paper
• Collaborative Regulation of Escherichia coli Glutamate-Dependent Acid Resistance by Two AraC-Like Regulators, GadX and GadW (YhiW)

  2002cited by this paper
• EnvZ-OmpR Interaction and Osmoregulation in Escherichia coli *

  2002cited by this paper
• A glutamate decarboxylase system protects Listeria monocytogenes in gastric fluid

  2001cited by this paper
• An activator of glutamate decarboxylase genes regulates the expression of enteropathogenic Escherichia coli virulence genes through control of the plasmid‐encoded regulator, Per

  2001cited by this paper
• Escherichia coli acid resistance: cAMP receptor protein and a 20 bp cis-acting sequence control pH and stationary phase expression of the gadA and gadBC glutamate decarboxylase genes.

  2001cited by this paper
• One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products.

  2000cited by this paper
• Nitrogen regulatory protein C-controlled genes of Escherichia coli: scavenging as a defense against nitrogen limitation.

  2000influential reference
• Control of Acid Resistance inEscherichia coli

  1999cited by this paper
• Membrane cyclopropane fatty acid content is a major factor in acid resistance of Escherichia coli

  1999cited by this paper
• A chloride‐inducible acid resistance mechanism in Lactococcus lactis and its regulation

  1998cited by this paper
• Molecular analysis of the regulation of csiD, a carbon starvation-inducible gene in Escherichia coli that is exclusively dependent on sigma s and requires activation by cAMP-CRP.

  1998cited by this paper
• The nac (Nitrogen Assimilation Control) Gene from Escherichia coli

  1998cited by this paper
• Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements.

  1997cited by this paper
• Mechanisms of acid resistance in enterohemorrhagic Escherichia coli

  1996cited by this paper
• Molecular characterization of adiY, a regulatory gene which affects expression of the biodegradative acid-induced arginine decarboxylase gene (adiA) of Escherichia coli.

  1996cited by this paper
• Growth and survival of Escherichia coli O157:H7 under acidic conditions

  1995cited by this paper
• Acid tolerance of enterohemorrhagic Escherichia coli

  1995cited by this paper
• A sigma 54 promoter and downstream sequence elements ftr2 and ftr3 are required for regulated expression of divergent transcription units flaN and flbG in Caulobacter crescentus

  1993cited by this paper
• Acid resistance in enteric bacteria

  1993cited by this paper
• Purification and initial characterization of AhrC: the regulator of arginine metabolism genes in Bacillus subtilis

  1992cited by this paper
• Control site location and transcriptional regulation in Escherichia coli

  1991cited by this paper
• Coexistence of the genes for putrescine transport protein and ornithine decarboxylase at 16 min on Escherichia coli chromosome.

  1991influential reference
• Nitrogen regulation system of Klebsiella aerogenes: the nac gene

  1983cited by this paper
• Influence of gastric acidity on bacterial and parasitic enteric infections. A perspective.

  1973cited by this paper
• Compounds Which Serve as the Sole Source of Carbon or Nitrogen for Salmonella typhimurium LT-2

  1969cited by this paper

• Condensation of the RNA chaperone Hfq is coupled to inhibition of carbon assimilation and contributes to the stabilisation of regulatory RNAs in nitrogen starved Escherichia coli

  2025cites this paper
• Predictive biophysical neural network modeling of a compendium of in vivo transcription factor DNA binding profiles for Escherichia coli

  2025cites this paper
• Fur-regulated urease contributes to the environmental adaptation of Yersinia pseudotuberculosis

  2025cites this paper
• PET-FBA: A Lightweight Enzyme Allocation and Thermodynamics-Constrained Flux Analysis Approach to Explore Escherichia coli Metabolic adaptation to Intracellular Acidification.

  2025cites this paper
• Condensation of the RNA chaperone Hfq is coupled to inhibition of glucose uptake and contributes to the stabilization of regulatory RNAs in nitrogen-starved Escherichia coli

  2025cites this paper
• Whole genome duplication drives transcriptome reprogramming in response to drought in alfalfa

  2025cites this paper
• Methods for studying microbial acid stress responses: from molecules to populations

  2024cites this paper
• Baccharoides anthelmintica (L.) Moench: A Review on Ethnomedicinal, Phytochemical, Pharmacological and Toxicological Profile

  2024cites this paper
• Achieving robust synthetic tolerance in industrial E. coli through negative auto-regulation of a DsrA-Hfq module

  2024cites this paper
• Multitier regulation of the E. coli extreme acid stress response by CsrA

  2024cites this paper
• RpoS and the bacterial general stress response

  2024cites this paper
• Genomic island-encoded LmiA regulates acid resistance and biofilm formation in enterohemorrhagic Escherichia coli O157:H7

  2024cites this paper
• Antimicrobial Activity of Glycyrrhizinic Acid Is pH-Dependent

  2024cites this paper
• A Cryptic Prophage Transcription Factor Drives Phenotypic Changes via Host Gene Regulation

  2024cites this paper
• Integrated multi-omics unveil the impact of H-phosphinic analogs of glutamate and α-ketoglutarate on Escherichia coli metabolism

  2024cites this paper
• Predictive Biophysical Neural Network Modeling of a Compendium of in vivo Transcription Factor DNA Binding Profiles for Escherichia coli

  2024cites this paper
• Bioinformatics-based diagnosis and evaluation of several pivotal genes and pathways associated with immune infiltration at different time points in spinal cord injury

  2023cites this paper
• Multilayered regulation of amino acid metabolism in Escherichia coli.

  2023cites this paper
• The Caulobacter NtrB-NtrC two-component system bridges nitrogen assimilation and cell development

  2023cites this paper
• The Caulobacter NtrB-NtrC two-component system bridges nitrogen assimilation and cell development

  2023cites this paper
• Enhancing Cancer Chemo‐Immunotherapy: Innovative Approaches for Overcoming Immunosuppression by Functional Nanomaterials

  2023cites this paper
• Pediococcus inopinatus with a well-developed CRISPR-Cas system dominates in long-term fermented kimchi, Mukeunji.

  2023cites this paper
• Enhancing Escherichia coli abiotic stress resistance through ornithine lipid formation

  2023cites this paper
• Ribosome profiling reveals the fine-tuned response of Escherichia coli to mild and severe acid stress

  2023cites this paper
• Expanded roles of lactate-sensing LldR in transcription regulation of the Escherichia coli K-12 genome: lactate utilisation and acid resistance

  2023cites this paper
• Transcription-replication interactions reveal principles of bacterial genome regulation

  2023cites this paper
• Purine catabolism by enterobacteria.

  2023cites this paper
• Model-driven experimental design workflow expands understanding of regulatory role of Nac in Escherichia coli

  2023influential citation
• Cooperative Interaction between Acid and Copper Resistance in Escherichia coli

  2022cites this paper
• More than Meets the Eye: Untargeted Metabolomics and Lipidomics Reveal Complex Pathways Spurred by Activation of Acid Resistance Mechanisms in Escherichia coli.

  2022cites this paper
• Glutamine synthetase mRNA releases sRNA from its 3′UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae

  2022cites this paper
• Auxotrophic and prototrophic conditional genetic networks reveal the rewiring of transcription factors in Escherichia coli

  2022cites this paper
• Transcription Factor SrsR (YgfI) Is a Novel Regulator for the Stress-Response Genes in Stationary Phase in Escherichia coli K-12

  2022cites this paper
• RegulonDB 11.0: Comprehensive high-throughput datasets on transcriptional regulation in Escherichia coli K-12

  2022cites this paper
• Is energy excess the initial trigger of carbon overflow metabolism? Transcriptional network response of carbon-limited Escherichia coli to transient carbon excess

  2022cites this paper
• Division of labor and collective functionality in Escherichia coli under acid stress

  2022cites this paper
• Regulation of Escherichia coli fim gene transcription by GadE and other acid tolerance gene products.

  2022cites this paper
• The Escherichia coli Amino Acid Uptake Protein CycA: Regulation of Its Synthesis and Practical Application in l-Isoleucine Production

  2022cites this paper
• Sensory Systems and Transcriptional Regulation in Escherichia coli

  2022cites this paper
• Virus–Host Interaction Gets Curiouser and Curiouser. PART II: Functional Transcriptomics of the E. coli DksA-Deficient Cell upon Phage P1vir Infection

  2021cites this paper
• Engineering of the Small Noncoding RNA (sRNA) DsrA Together with the sRNA Chaperone Hfq Enhances the Acid Tolerance of Escherichia coli

  2021cites this paper
• The leucine-responsive regulatory proteins/feast-famine regulatory proteins: an ancient and complex class of transcriptional regulators in bacteria and archaea

  2021cites this paper
• Tolerance to Glutaraldehyde in Escherichia coli Mediated by Overexpression of the Aldehyde Reductase YqhD by YqhC

  2021cites this paper
• The EcoCyc Database in 2021

  2021cites this paper
• Cellular Effects of 2′,3′-Cyclic Nucleotide Monophosphates in Gram-Negative Bacteria

  2021cites this paper
• Cellular Effects of 2 ́,3 ́-Cyclic Nucleotide Monophosphates in Gram-Negative 1 Bacteria 2 3

  2021cites this paper
• Artificial intelligence and machine learning in precision and genomic medicine

  2021cites this paper
• Correlation between faecal microbial taxa and ulcerative colitis in different phases of disease activity in a north Indian cohort

  2021cites this paper
• Improving Analysis and Annotation of Microarray Data with Protein Interactions.

  2021cites this paper
• Multicellular immune dynamics implicate PIM1 as a potential therapeutic target for uveitis

  2021cites this paper
• Network Analysis of Large-Scale Data and Its Application to Immunology.

  2020cites this paper
• Effect of particle size and surface charge of nanoparticles in penetration through intestinal mucus barrier

  2020cites this paper
• Overcoming Drug Resistance to BRAF Inhibitor

  2020cites this paper
• How Should Cancer Models Be Constructed?

  2020cites this paper
• Epigenetic competition reveals density-dependent regulation and target site plasticity of phosphorothioate epigenetics in bacteria

  2020cites this paper
• Molecular Design of a Signaling System Influences Noise in Protein Abundance under Acid Stress in Different Gammaproteobacteria

  2020cites this paper
• References

  2020cites this paper
• RNase E-dependent degradation of tnaA mRNA encoding tryptophanase is prerequisite for the induction of acid resistance in Escherichia coli

  2020cites this paper
• Meloxicam encapsulated nanostructured colloidal self-assembly for evaluating antitumor and anti-inflammatory efficacy in 3D printed scaffolds.

  2020cites this paper
• The Adaptive Response to Long-Term Nitrogen Starvation in Escherichia coli Requires the Breakdown of Allantoin

  2020cites this paper
• Genome-wide targets identification by CRISPRi-Omics for high-titer production of free fatty acids in Escherichia coli

  2020cites this paper
• The Adaptive Response to Long-Term Nitrogen Starvation in Escherichia coli Requires the Breakdown of Allantoin

  2020cites this paper
• Metabolic Traits of Bovine Shiga Toxin-Producing Escherichia coli (STEC) Strains with Different Colonization Properties

  2020cites this paper
• Core and Accessory Genome Comparison of Australian and International Strains of O157 Shiga Toxin-Producing Escherichia coli

  2020cites this paper
• Disrupting the ArcA regulatory network increases tetracycline susceptibility of TetR Escherichia coli

  2020cites this paper
• A Novel Butanol Tolerance-Promoting Function of the Transcription Factor Rob in Escherichia coli

  2020cites this paper
• The transition of Rhodobacter sphaeroides into a microbial cell factory

  2020cites this paper
• The impact of cell structure, metabolism and group behavior for the survival of bacteria under stress conditions

  2020cites this paper
• Plastic Circuits: Regulatory Flexibility in Fine Tuning Pathogen Success.

  2020cites this paper
• Limits to a classic paradigm: most transcription factors in E. coli regulate genes involved in multiple biological processes

  2019cites this paper
• How to schedule VEGF and PD-1 inhibitors in combination cancer therapy?

  2019cites this paper
• Yeast Expression Systems: Overview and Recent Advances

  2019cites this paper
• Integrating Bacterial ChIP‐seq and RNA‐seq Data With SnakeChunks

  2019cites this paper
• Systems biology informed deep learning for inferring parameters and hidden dynamics

  2019cites this paper
• Population-based meta-heuristic for active modules identification

  2019cites this paper
• Single-cell protein profiling in microchambers with barcoded beads

  2019cites this paper
• Through the eyes of a pathogen: light perception and signal transduction in Acinetobacter baumannii

  2019cites this paper
• Estimation of Transcription Factor Activity in Knockdown Studies

  2019cites this paper
• Function and Regulation of Acid Resistance Antiporters

  2019cites this paper
• Biological Parts for Kluyveromyces marxianus Synthetic Biology

  2019cites this paper
• Sigma Factor-Mediated Tuning of Bacterial Cell-Free Synthetic Genetic Oscillators

  2018cites this paper
• The antibiotics potentiator bicarbonate causes upregulation of tryptophanase and iron acquisition proteins in Escherichia coli

  2018cites this paper
• Estimation methods for heterogeneous cell population models in systems biology

  2018cites this paper
• Controller protein of restriction–modification system Kpn2I affects transcription of its gene by acting as a transcription elongation roadblock

  2018cites this paper
• Advances in metabolic modeling of oleaginous microalgae

  2018cites this paper
• Statistical relationship between metabolic decomposition and chemical uptake predicts bioconcentration factor data for diverse chemical exposures

  2018cites this paper
• Proteome analysis of an Escherichia coli ptsN-null strain under different nitrogen regimes.

  2018cites this paper
• Biofilms in the Food Industry: Health Aspects and Control Methods

  2018cites this paper
• ATG13 dynamics in nonselective autophagy and mitophagy: insights from live imaging studies and mathematical modeling

  2018cites this paper
• Genomic and phenotypic comparison of Lactobacillus reuteri isolates from food and intestinal ecosystems provides insights to probiotic applications

  2018cites this paper
• Limits to a classic paradigm: Most transcription factors regulate genes in multiple biological processes

  2018cites this paper
• Costless metabolic secretions as drivers of interspecies interactions in microbial ecosystems

  2018cites this paper
• Clostridium butyricum population balance model: Predicting dynamic metabolic flux distributions using an objective function related to extracellular glycerol content

  2018cites this paper
• New insights into the adaptive transcriptional response to nitrogen starvation in Escherichia coli

  2018cites this paper
• A microfluidic co-cultivation platform to investigate microbial interactions at defined microenvironments.

  2018cites this paper
• Studying Glycolytic Oscillations in Individual Yeast Cells by Combining Fluorescence Microscopy with Microfluidics and Optical Tweezers

  2018cites this paper
• A unified resource for transcriptional regulation in Escherichia coli K-12 incorporating high-throughput-generated binding data into RegulonDB version 10.0

  2018cites this paper
• Genome-scale modeling of yeast: chronology, applications and critical perspectives

  2017cites this paper
• Features of CRISPR-Cas Regulation Key to Highly Efficient and Temporally-Specific crRNA Production

  2017cites this paper
• Towards a unified resource for transcriptional regulation in Escherichia coli K-12: Incorporating high throughput-generated binding data within the classic framework of regulation of initiation of transcription in RegulonDB

  2017cites this paper