Roles of reactive oxygen species-degrading enzymes of Francisella tularensis SCHU S4

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Journal titleInfection and Immunity
Pages22552263; # of pages: 9
Subjectalkyl hydroperoxide reductase subunit c; bacterial enzyme; catalase; glutathione peroxidase; hydrogen peroxide; live vaccine; paraquat; peroxidase; peroxynitrite; reactive oxygen metabolite; animal cell; animal experiment; animal model; bacterial gene; bacterial strain; bacterial survival; bacterial viability; bacterial virulence; bacterium identification; bacterium mutant; bone marrow derived macrophage; cell division; colony forming unit; detoxification; Francisella tularensis; gene deletion; macrophage; protein expression; protein function; tularemia
AbstractFrancisella tularensis is a facultative intracellular bacterium utilizing macrophages as its primary intracellular habitat and is therefore highly capable of resisting the effects of reactive oxygen species (ROS), potent mediators of the bactericidal activity of macrophages. We investigated the roles of enzymes presumed to be important for protection against ROS. Four mutants of the highly virulent SCHU S4 strain with deletions of the genes encoding catalase (katG), glutathione peroxidase (gpx), a DyP-type peroxidase (FTT0086), or double deletion of FTT0086 and katG showed much increased susceptibility to hydrogen peroxide (H<inf>2</inf>O<inf>2</inf>) and slightly increased susceptibility to paraquat but not to peroxynitrite (ONOO-) and displayed intact intramacrophage replication. Nevertheless, mice infected with the double deletion mutant showed significantly longer survival than SCHU S4-infected mice. Unlike the aforementioned mutants, deletion of the gene coding for alkyl-hydroperoxide reductase subunit C (ahpC) generated a mutant much more susceptible to paraquat and ONOO- but not to H<inf>2</inf>O<inf>2</inf>. It showed intact replication in J774 cells but impaired replication in bone marrow-derived macrophages and in internal organs of mice. The live vaccine strain, LVS, is more susceptible than virulent strains to ROS-mediated killing and possesses a truncated form of FTT0086. Expression of the SCHU S4 FTT0086 gene rendered LVS more resistant to H<inf>2</inf>O<inf>2</inf>, which demonstrates that the SCHU S4 strain possesses additional detoxifying mechanisms. Collectively, the results demonstrate that SCHU S4 ROS-detoxifying enzymes have overlapping functions, and therefore, deletion of one or the other does not critically impair the intracellular replication or virulence, although AhpC appears to have a unique function.
Publication date
PublisherAmerican Society for Microbiology
AffiliationNational Research Council Canada (NRC-CNRC); Human Health Therapeutics
Peer reviewedYes
NPARC number21275619
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Record identifier13e4ad88-3140-4ab2-8cc8-63e292af6b94
Record created2015-07-14
Record modified2016-05-09
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