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Open Access Research article

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

Eduardo H Morales134, Bernardo Collao1, Prerak T Desai2, Iván L Calderón1, Fernando Gil1, Roberto Luraschi1, Steffen Porwollik2, Michael McClelland2 and Claudia P Saavedra1*

  • * Corresponding author: Claudia P Saavedra csaavedra@unab.cl

  • † Equal contributors

Author Affiliations

1 Laboratorio de Microbiología Molecular, Facultad Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile

2 Department of Microbiology and Molecular Genetics, B240 Medical Sciences Building, University of California, Irvine, CA 92697, USA

3 Present address: Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA

4 Present address: Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA

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BMC Genomics 2013, 14:626  doi:10.1186/1471-2164-14-626

Published: 17 September 2013

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.

Keywords:
ArcAB two-component system; Oxidative stress; Hydrogen peroxide resistance