Redundant Hydrogen Peroxide Scavengers Contribute to Salmonella Virulence and Oxidative Stress Resistance
- 15 July 2009
- journal article
- research article
- Published by American Society for Microbiology in Journal of Bacteriology
- Vol. 191 (14), 4605-4614
- https://doi.org/10.1128/jb.00144-09
Abstract
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 (H 2 O 2 ) can diffuse across bacterial membranes and damage biomolecules. Genome analysis allowed us to identify five genes encoding H 2 O 2 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 H 2 O 2 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 H 2 O 2 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 H 2 O 2 and contribute to the virulence. This enzymatic redundancy highlights the evolutionary strategies developed by bacterial pathogens to survive within hostile environments.Keywords
This publication has 48 references indexed in Scilit:
- Phagocytic Superoxide Specifically Damages an Extracytoplasmic Target to Inhibit or Kill SalmonellaPLOS ONE, 2009
- Physiological and Regulatory Characterization of KatA and KatY inYersinia pestisDNA and Cell Biology, 2008
- Substrate specificity and redox potential of AhpC, a bacterial peroxiredoxinProceedings of the National Academy of Sciences of the United States of America, 2008
- Neisseria gonorrhoeae Catalase Is Not Required for Experimental Genital Tract Infection despite the Induction of a Localized Neutrophil ResponseInfection and Immunity, 2007
- Resistance ofFrancisella tularensisStrains against Reactive Nitrogen and Oxygen Species with Special Reference to the Role of KatGInfection and Immunity, 2007
- In vitro and in vivo characterization of alkyl hydroperoxide reductase mutant strains of Helicobacter hepaticusBiochimica et Biophysica Acta (BBA) - General Subjects, 2007
- Catalase (KatA) and Alkyl Hydroperoxide Reductase (AhpC) Have Compensatory Roles in Peroxide Stress Resistance and Are Required for Survival, Persistence, and Nasal Colonization inStaphylococcus aureusJournal of Bacteriology, 2007
- Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella entericaMolecular Microbiology, 2002
- Essential Thioredoxin-Dependent Peroxiredoxin System from Helicobacter pylori : Genetic and Kinetic CharacterizationJournal of Bacteriology, 2001
- DNA repair is more important than catalase for Salmonella virulence in mice.JCI Insight, 1995