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The Transcription Factor ArcA Modulates Salmonella’s Metabolism In Response To Neutrophil Hypochlorous Acid-Mediated Stress
C. Pardo-Esté, Juan Castro-Severyn, G. I. Krüger, C. E. Cabezas, A. Briones, Camila Aguirre, Naiyulin Morales, Maria Soledad Baquedano, Y. Sulbaran, Alejandro A. Hidalgo, C. Meneses, Ignacio Poblete-Castro, E. Castro-Nallar, M. Valvano, C. Saavedra
Published 2019 · Chemistry, Medicine
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Salmonella Typhimurium, a bacterial pathogen with high metabolic plasticity, can adapt to different environmental conditions; these traits enhance its virulence by enabling bacterial survival. Neutrophils play important roles in the innate immune response, including the production of microbicidal reactive oxygen species (ROS). In addition, the myeloperoxidase in neutrophils catalyzes the formation of hypochlorous acid (HOCl), a highly toxic molecule that reacts with essential biomolecules, causing oxidative damage including lipid peroxidation and protein carbonylation. The bacterial response regulator ArcA regulates adaptive responses to oxygen levels and influences the survival of Salmonella inside phagocytic cells. Here, we demonstrate by whole transcriptomic analyses that ArcA regulates genes related to various metabolic pathways, enabling bacterial survival during HOCl-stress in vitro. Also, inside neutrophils, ArcA controls the transcription of several metabolic pathways by downregulating the expression of genes related to fatty acid degradation, lysine degradation, and arginine, proline, pyruvate, and propanoate metabolism. ArcA also upregulates genes encoding components of the oxidative pathway. These results underscore the importance of ArcA in ATP generation inside the neutrophil phagosome and its participation in bacterial metabolic adaptations during HOCl stress.
This paper references
Quality control and preprocessing of metagenomic datasets
R. Schmieder (2011)
Quality control and preprocessing of meta
R. Edwards (2011)
An Incomplete TCA Cycle Increases Survival of Salmonella Typhimurium during Infection of Resting and Activated Murine Macrophages
Steven D. Bowden (2010)
Role of Host Cell-Derived Amino Acids in Nutrition of Intracellular Salmonella enterica
J. Popp (2015)
Conflicting roles for a cell surface modification in Salmonella
John F. May (2013)
Glucose and Glycolysis Are Required for the Successful Infection of Macrophages and Mice by Salmonella enterica Serovar Typhimurium
Steven D. Bowden (2009)
Salmonella typhimurium mutants that downregulate phagocyte nitric oxide production
S. Eriksson (2000)
The challenge of relating gene expression to the virulence of Salmonella enterica serovar Typhimurium.
Magali Hébrard (2011)
RNA-seq Brings New Insights to the Intra-Macrophage Transcriptome of Salmonella Typhimurium
S. Srikumar (2015)
Cytoscape: a software environment for integrated models of biomolecular interaction networks.
P. Shannon (2003)
Response regulator ArcA of Salmonella enterica serovar Typhimurium downregulates expression of OmpD, a porin facilitating uptake of hydrogen peroxide.
I. Calderón (2011)
Analysis of the ArcA regulon in anaerobically grown Salmonella enterica sv. Typhimurium
M. R. Evans (2010)
Salmonella – the ultimate insider. Salmonella virulence factors that modulate intracellular survival
J. A. Ibarra (2009)
Absolute rate constants for the reaction of hypochlorous acid with protein side chains and peptide bonds.
D. Pattison (2001)
ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks
G. Bindea (2009)
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data
M. Robinson (2010)
Transcriptomic Responses of Salmonella enterica Serovars Enteritidis and Typhimurium to Chlorine-Based Oxidative Stress
Siyun Wang (2010)
Differential susceptibility of plasma proteins to oxidative modification: examination by western blot immunoassay.
E. Shacter (1994)
Myeloperoxidase in human peripheral blood
R C. (2016)
Determination of carbonyl content in oxidatively modified proteins.
R. L. Levine (1990)
FastQC a Quality-Control Tool for High-Throughput Sequence
S. Andrews (2010)
pheatmap: Pretty Heatmaps. R Package Version 1.0.8
R. Kolde (2015)
Advances in molecular genetic systems in malaria
T. D. Koning-Ward (2015)
Neutrophil-generated oxidative stress
W. N. 5699-5704.1991 Beavers (2016)
Bacterial responses to reactive
M. J. jlb.47.1.79 Gray (2013)
Hypochlorous acid and hydrogen peroxide-induced negative regulation of Salmonella enterica serovar Typhimurium ompW by the response regulator ArcA
E. H. Morales (2012)
Cationic Amino Acid Transporters and Salmonella Typhimurium ArgT Collectively Regulate Arginine Availability towards Intracellular Salmonella Growth
Priyanka Das (2010)
Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica
S. Eriksson (2003)
Isolation, purification and labeling of mouse bone marrow neutrophils for functional studies and adoptive transfer experiments.
Muthulekha Swamydas (2013)
The infectious intracellular lifestyle of Salmonella enterica relies on the adaptation to nutritional conditions within the Salmonella-containing vacuole
L. Diacovich (2017)
Metabolomic and transcriptomic stress
D Steinhauser (2010)
Proteomic Delineation of the ArcA Regulon in Salmonella Typhimurium During Anaerobiosis*
Zhen Wang (2018)
Control of Lipoprotein Lipase Secretion by Macrophages: Effect of Macrophage Differentiation Agents
R. Goldman (1990)
The transcription factor SlyA from Salmonella Typhimurium regulates genes in response to hydrogen peroxide and sodium hypochlorite.
C. E. Cabezas (2018)
edgeR: a Bioconductor
M. D. Robinson (2010)
Salmonella enterica Serovar Typhimurium Skills To Succeed in the Host: Virulence and Regulation
A. Fàbrega (2013)
A Comparison of the ATP Generating Pathways Used by S. Typhimurium to Fuel Replication within Human and Murine Macrophage and Epithelial Cell Lines
Enriqueta Garcia-Gutierrez (2016)
Salmonella pathogenicity island 2-dependent evasion of the phagocyte NADPH oxidase.
A. Vazquez-Torres (2000)
Hypochlorite-induced damage to DNA
C. L. Hawkins (2002)
Metabolomic and transcriptomic stress response of Escherichia coli
S. Jozefczuk (2010)
Effect of oxygen, and ArcA and FNR regulators on the expression of genes related to the electron transfer chain and the TCA cycle in Escherichia coli.
Sagit Shalel-Levanon (2005)
Regulation by a novel protein of the bimodal distribution of lipopolysaccharide in the outer membrane of Escherichia coli.
R. Batchelor (1991)
Comprehensive Identification of Salmonella enterica Serovar Typhimurium Genes Required for Infection of BALB/c Mice
R. Chaudhuri (2009)
Bacterial responses to reactive chlorine species.
M. J. Gray (2013)
Salmonella–Host Interactions – Modulation of the Host Innate Immune System
Daniel Hurley (2014)
A new mathematical model for relative quantification in real-time RT-PCR.
M. Pfaffl (2001)
Metabolic Response of Escherichia coli upon Treatment with Hypochlorite at Sub-Lethal Concentrations
A. Drazic (2015)
Redox reactions and microbial killing in the neutrophil phagosome.
C. Winterbourn (2013)
R Package "corrplot": Visualization of a Correlation Matrix
T Wei (2017)
Biosynthesis and export of bacterial lipopolysaccharides.
C. Whitfield (2014)
Identification of the promotors directing in vivo expression of hemolysin genes in Proteus vulgaris and Escherichia coli
V. Koronakis (2004)
The ArcAB two-component regulatory system promotes resistance to reactive oxygen species and systemic infection by Salmonella Typhimurium (vol 13, e0203497, 2018): The ArcAB two-component regulatory system promotes resistance to reactive oxygen species and systemic infection by Salmonella Typhimuriu
Coral Pardo-Esté (2019)
Exploiting host immunity: the Salmonella paradigm.
Judith Behnsen (2015)
The ArcAB two-component regulatory system promotes resistance to reactive oxygen species and systemic infection by Salmonella Typhimurium
Coral Pardo-Esté (2018)
Neutrophil-generated oxidative stress and protein damage in Staphylococcus aureus.
William N Beavers (2016)
Generation of a reference transcriptome for evaluating rainbow trout responses to various stressors
C. C. Sánchez (2011)
FastQC a Quality-Control Tool for High-Throughput Sequence Data
Mechanisms of actions of sodium hypochlorite in cleaning and disinfection processes.
S. Fukuzaki (2006)
Salmonella's long-term relationship with its host.
T. Ruby (2012)
PhoP/PhoQ: macrophage‐specific modulators of Salmonella virulence?
S. Miller (1991)
HTSeq—a Python framework
S. Anders (2015)
Absolute rate constants
M. J. Davies (2001)
A new mathematical model for relative quantification
M. W. Pfaffl (2011)
The Bacterial Response Regulator ArcA Uses a Diverse Binding Site Architecture to Regulate Carbon Oxidation Globally
Dan M Park (2013)
Deletions in the pyruvate pathway of Salmonella Typhimurium alter SPI1-mediated gene expression and infectivity
J. Abernathy (2012)
Fast gapped-read alignment with Bowtie 2
B. Langmead (2012)
Salmonellae interactions with host processes
Doris L. LaRock (2015)
HTSeq—a Python framework to work with high-throughput sequencing data
S. Anders (2015)
Signal transduction pathway mediated by the novel regulator LoiA for low oxygen tension induced Salmonella Typhimurium invasion
Lingyan Jiang (2017)
Trafficking of the Salmonella Vacuole in Macrophages
D. Holden (2002)
Identification of a Hypochlorite-specific Transcription Factor from Escherichia coli*
Katharina M. Gebendorfer (2012)
Participation of the Salmonella OmpD Porin in the Infection of RAW264.7 Macrophages and BALB/c Mice
F. Ipinza (2014)
Myeloperoxidase in human peripheral blood lymphocytes: Production and subcellular localization.
S. Okada (2016)
The oxidative environment and protein damage.
M. Davies (2005)
A comparison of the ATP generating pathways used by S. Typhimurium to fuel replication within human and murine macrophage Frontiers in Microbiology
E. Garcia-Gutierrez (2016)
M J. (2011)
M. S. Lionakis (2013)
Hypochlorite-induced damage to DNA, RNA, and polynucleotides: formation of chloramines and nitrogen-centered radicals.
C. Hawkins (2002)
Critical roles of neutrophils in host defense against experimental systemic infections of mice by Listeria monocytogenes, Salmonella typhimurium, and Yersinia enterocolitica.
J. Conlan (1997)
Non-canonical activation of OmpR drives acid and osmotic stress responses in single bacterial cells
Smarajit Chakraborty (2017)
Probing the ArcA regulon under aerobic/ROS conditions in Salmonella enterica serovar Typhimurium
E. H. Morales (2013)
Myeloperoxidase-dependent Lipid Peroxidation Promotes the Oxidative Modification of Cytosolic Proteins in Phagocytic Neutrophils*
Rachel P. Wilkie-Grantham (2015)
Salmonella–the ultimate insider
J. A. Ibarra (2009)
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