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Published on: March 7, 2019
Cytochrome c peroxidase contributes to the antioxidant defense of Cryptococcus neoformans
Steven S Giles1, John R Perfect, Gary M Cox
1Departments of Medicine and Molecular Genetics and Microbiology, Duke University Medical Center, P.O. Box 3353, Durham, NC 27710, USA.
Abstract:
Cryptococcus neoformans is an opportunistic pathogen and the leading cause of fungal meningitis. To survive within the host, this organism must be able to protect itself from oxidative stress. Cytochrome c peroxidase (Ccp1) is a mitochondrial antioxidant that catalyzes the degradation of hydrogen peroxide. In the present study, we characterized the contribution of the C. neoformans Ccp1 to antioxidant defense and for virulence. Consistent with studies of Ccp1 function in Sacchromyces cerevisiae, we found that Ccp1 contributes to resistance against exogenous oxidative stress in vitro. However, the oxidative stress phenotype does not diminish the virulence of ccp1 mutant strains in a murine model of C. neoformans disease. These results suggest that Ccp1 is involved in a complex system of protection against exogenous oxidative stress and that the elimination of this component of the antioxidant defense system does not diminish the virulence of C. neoformans.
Insights
Cytochrome c peroxidase (Ccp1) aids Cryptococcus neoformans in resisting oxidative stress in lab tests. However, removing Ccp1 did not reduce the fungus's ability to cause disease in mice.
Area of Science:
- Mycology
- Pathogen Biology
- Antioxidant Research
Background:
- Cryptococcus neoformans is a major cause of fungal meningitis.
- Host survival requires defense against oxidative stress.
- Cytochrome c peroxidase (Ccp1) is a key mitochondrial antioxidant enzyme.
Purpose of the Study:
- To investigate the role of Ccp1 in Cryptococcus neoformans antioxidant defense.
- To determine the contribution of Ccp1 to fungal virulence.
Main Methods:
- In vitro assays to assess oxidative stress resistance.
- Murine model of cryptococcosis to evaluate virulence.
Main Results:
- Ccp1 enhances resistance to exogenous oxidative stress in vitro, similar to findings in Saccharomyces cerevisiae.
- ccp1 mutant strains showed no significant decrease in virulence in a murine model of disease.
Conclusions:
- Ccp1 is part of a complex antioxidant defense system in C. neoformans.
- Eliminating Ccp1 does not compromise the virulence of C. neoformans in a host environment.
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