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Journal of Bacteriology, July 2009, p. 4605-4614, Vol. 191, No. 14
0021-9193/09/$08.00+0     doi:10.1128/JB.00144-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Redundant Hydrogen Peroxide Scavengers Contribute to Salmonella Virulence and Oxidative Stress Resistance{triangledown} ,{dagger}

Magali Hébrard,1,3 Julie P. M. Viala,1,3 Stéphane Méresse,2,3 Frédéric Barras,1,3 and Laurent Aussel1,3*

CNRS, Laboratoire de Chimie Bactérienne (UPR 9043), Institut de Microbiologie de la Méditerranée, IFR 88, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France,1 Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Univ. Méditerranée, Parc Scientifique de Luminy, Case 906, 13288 Marseille Cedex 9, France,2 Aix-Marseille University, Marseille, France3

Received 3 February 2009/ Accepted 9 May 2009

Salmonella enterica serovar Typhimurium is an intracellular pathogen that can survive and replicate within macrophages. One of the host defense mechanisms that Salmonella encounters during infection is the production of reactive oxygen species by the phagocyte NADPH oxidase. Among them, hydrogen peroxide (H2O2) can diffuse across bacterial membranes and damage biomolecules. Genome analysis allowed us to identify five genes encoding H2O2 degrading enzymes: three catalases (KatE, KatG, and KatN) and two alkyl hydroperoxide reductases (AhpC and TsaA). Inactivation of the five cognate structural genes yielded the HpxF– mutant, which exhibited a high sensitivity to exogenous H2O2 and a severe survival defect within macrophages. When the phagocyte NADPH oxidase was inhibited, its proliferation index increased 3.7-fold. Moreover, the overexpression of katG or tsaA in the HpxF– background was sufficient to confer a proliferation index similar to that of the wild type in macrophages and a resistance to millimolar H2O2 in rich medium. The HpxF– mutant also showed an attenuated virulence in a mouse model. These data indicate that Salmonella catalases and alkyl hydroperoxide reductases are required to degrade H2O2 and contribute to the virulence. This enzymatic redundancy highlights the evolutionary strategies developed by bacterial pathogens to survive within hostile environments.

* Corresponding author. Mailing address: Laboratoire de Chimie Bactérienne, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France. Phone: 33 4 91 16 46 59. Fax: 33 4 91 71 89 14. E-mail: aussel{at}ifr88.cnrs-mrs.fr

{triangledown} Published ahead of print on 15 May 2009.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

Journal of Bacteriology, July 2009, p. 4605-4614, Vol. 191, No. 14
0021-9193/09/$08.00+0     doi:10.1128/JB.00144-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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