Probing the ArcA regulon under aerobic/ROS conditions in Salmonella enterica serovar Typhimurium

Eduardo H. Morales, Bernardo Collao, Prerak T. Desai, Iván L. Calderón, Fernando Gil, Roberto Luraschi, Steffen Porwollik, Michael McClelland, Claudia P. Saavedra

Resultado de la investigación: Article

10 Citas (Scopus)

Resumen

Background: Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS), which is part of the oxidative burst encountered upon internalization of Salmonella enterica serovar Typhimurium (S. Typhimurium) by phagocytic cells. It has previously been established that, the ArcAB two-component system plays a critical role in ROS resistance, but the genes regulated by the system remained undetermined to date. We therefore investigated the ArcA regulon in aerobically growing S. Typhimurium before and after exposure to H2O2 by querying gene expression and other physiological changes in wild type and ΔarcA strains.Results: In the ΔarcA strain, expression of 292 genes showed direct or indirect regulation by ArcA in response to H2O2, of which 141were also regulated in aerobiosis, but in the opposite direction. Gene set enrichment analysis (GSEA) of the expression data from WT and ΔarcA strains, revealed that, in response to H2O2 challenge in aerobically grown cells, ArcA down regulated multiple PEP-PTS and ABC transporters, while up regulating genes involved in glutathione and glycerolipid metabolism and nucleotide transport. Further biochemical analysis guided by GSEA results showed that deletion of arcA during aerobic growth lead to increased reactive oxygen species (ROS) production which was concomitant with an increased NADH/NAD+ ratio. In absence of ArcA under aerobic conditions, H2O2 exposure resulted in lower levels of glutathione reductase activity, leading to a decreased GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio.Conclusion: The ArcA regulon was defined in 2 conditions, aerobic growth and the combination of peroxide treatment and aerobic growth in S. Typhimurium. ArcA coordinates a response that involves multiple aspects of the carbon flux through central metabolism, which ultimately modulates the reducing potential of the cell.

Idioma originalEnglish
Número de artículo626
PublicaciónBMC Genomics
Volumen14
N.º1
DOI
EstadoPublished - 17 sep 2013

Huella dactilar

Regulon
Salmonella enterica
Reactive Oxygen Species
Glutathione Disulfide
NAD
Genes
Glutathione
Aerobiosis
Growth
Gene Expression
Carbon Cycle
ATP-Binding Cassette Transporters
Respiratory Burst
Glutathione Reductase
Peroxides
Phagocytes
Hydrogen Peroxide
Nucleotides
Serogroup

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Citar esto

Morales, Eduardo H. ; Collao, Bernardo ; Desai, Prerak T. ; Calderón, Iván L. ; Gil, Fernando ; Luraschi, Roberto ; Porwollik, Steffen ; McClelland, Michael ; Saavedra, Claudia P. / Probing the ArcA regulon under aerobic/ROS conditions in Salmonella enterica serovar Typhimurium. En: BMC Genomics. 2013 ; Vol. 14, N.º 1.
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title = "Probing the ArcA regulon under aerobic/ROS conditions in Salmonella enterica serovar Typhimurium",
abstract = "Background: Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS), which is part of the oxidative burst encountered upon internalization of Salmonella enterica serovar Typhimurium (S. Typhimurium) by phagocytic cells. It has previously been established that, the ArcAB two-component system plays a critical role in ROS resistance, but the genes regulated by the system remained undetermined to date. We therefore investigated the ArcA regulon in aerobically growing S. Typhimurium before and after exposure to H2O2 by querying gene expression and other physiological changes in wild type and ΔarcA strains.Results: In the ΔarcA strain, expression of 292 genes showed direct or indirect regulation by ArcA in response to H2O2, of which 141were also regulated in aerobiosis, but in the opposite direction. Gene set enrichment analysis (GSEA) of the expression data from WT and ΔarcA strains, revealed that, in response to H2O2 challenge in aerobically grown cells, ArcA down regulated multiple PEP-PTS and ABC transporters, while up regulating genes involved in glutathione and glycerolipid metabolism and nucleotide transport. Further biochemical analysis guided by GSEA results showed that deletion of arcA during aerobic growth lead to increased reactive oxygen species (ROS) production which was concomitant with an increased NADH/NAD+ ratio. In absence of ArcA under aerobic conditions, H2O2 exposure resulted in lower levels of glutathione reductase activity, leading to a decreased GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio.Conclusion: The ArcA regulon was defined in 2 conditions, aerobic growth and the combination of peroxide treatment and aerobic growth in S. Typhimurium. ArcA coordinates a response that involves multiple aspects of the carbon flux through central metabolism, which ultimately modulates the reducing potential of the cell.",
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Probing the ArcA regulon under aerobic/ROS conditions in Salmonella enterica serovar Typhimurium. / Morales, Eduardo H.; Collao, Bernardo; Desai, Prerak T.; Calderón, Iván L.; Gil, Fernando; Luraschi, Roberto; Porwollik, Steffen; McClelland, Michael; Saavedra, Claudia P.

En: BMC Genomics, Vol. 14, N.º 1, 626, 17.09.2013.

Resultado de la investigación: Article

TY - JOUR

T1 - Probing the ArcA regulon under aerobic/ROS conditions in Salmonella enterica serovar Typhimurium

AU - Morales, Eduardo H.

AU - Collao, Bernardo

AU - Desai, Prerak T.

AU - Calderón, Iván L.

AU - Gil, Fernando

AU - Luraschi, Roberto

AU - Porwollik, Steffen

AU - McClelland, Michael

AU - Saavedra, Claudia P.

PY - 2013/9/17

Y1 - 2013/9/17

N2 - Background: Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS), which is part of the oxidative burst encountered upon internalization of Salmonella enterica serovar Typhimurium (S. Typhimurium) by phagocytic cells. It has previously been established that, the ArcAB two-component system plays a critical role in ROS resistance, but the genes regulated by the system remained undetermined to date. We therefore investigated the ArcA regulon in aerobically growing S. Typhimurium before and after exposure to H2O2 by querying gene expression and other physiological changes in wild type and ΔarcA strains.Results: In the ΔarcA strain, expression of 292 genes showed direct or indirect regulation by ArcA in response to H2O2, of which 141were also regulated in aerobiosis, but in the opposite direction. Gene set enrichment analysis (GSEA) of the expression data from WT and ΔarcA strains, revealed that, in response to H2O2 challenge in aerobically grown cells, ArcA down regulated multiple PEP-PTS and ABC transporters, while up regulating genes involved in glutathione and glycerolipid metabolism and nucleotide transport. Further biochemical analysis guided by GSEA results showed that deletion of arcA during aerobic growth lead to increased reactive oxygen species (ROS) production which was concomitant with an increased NADH/NAD+ ratio. In absence of ArcA under aerobic conditions, H2O2 exposure resulted in lower levels of glutathione reductase activity, leading to a decreased GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio.Conclusion: The ArcA regulon was defined in 2 conditions, aerobic growth and the combination of peroxide treatment and aerobic growth in S. Typhimurium. ArcA coordinates a response that involves multiple aspects of the carbon flux through central metabolism, which ultimately modulates the reducing potential of the cell.

AB - Background: Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS), which is part of the oxidative burst encountered upon internalization of Salmonella enterica serovar Typhimurium (S. Typhimurium) by phagocytic cells. It has previously been established that, the ArcAB two-component system plays a critical role in ROS resistance, but the genes regulated by the system remained undetermined to date. We therefore investigated the ArcA regulon in aerobically growing S. Typhimurium before and after exposure to H2O2 by querying gene expression and other physiological changes in wild type and ΔarcA strains.Results: In the ΔarcA strain, expression of 292 genes showed direct or indirect regulation by ArcA in response to H2O2, of which 141were also regulated in aerobiosis, but in the opposite direction. Gene set enrichment analysis (GSEA) of the expression data from WT and ΔarcA strains, revealed that, in response to H2O2 challenge in aerobically grown cells, ArcA down regulated multiple PEP-PTS and ABC transporters, while up regulating genes involved in glutathione and glycerolipid metabolism and nucleotide transport. Further biochemical analysis guided by GSEA results showed that deletion of arcA during aerobic growth lead to increased reactive oxygen species (ROS) production which was concomitant with an increased NADH/NAD+ ratio. In absence of ArcA under aerobic conditions, H2O2 exposure resulted in lower levels of glutathione reductase activity, leading to a decreased GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio.Conclusion: The ArcA regulon was defined in 2 conditions, aerobic growth and the combination of peroxide treatment and aerobic growth in S. Typhimurium. ArcA coordinates a response that involves multiple aspects of the carbon flux through central metabolism, which ultimately modulates the reducing potential of the cell.

KW - ArcAB two-component system

KW - Hydrogen peroxide resistance

KW - Oxidative stress

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U2 - 10.1186/1471-2164-14-626

DO - 10.1186/1471-2164-14-626

M3 - Article

C2 - 24044554

AN - SCOPUS:84883882146

VL - 14

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

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