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Comparative sensitivity of Histoplasma capsulatum conidiospores and blastospores to oxidative antifungal systems
Abstract:
The comparative sensitivity of blastospores and conidiospores of Histoplasma capsulatum to hydrogen peroxide, to hydrogen peroxide and halides, and to a combination of hydrogen peroxide and halide with the enzyme myeloperoxidase was studied. Blastospores of different strains of H. capsulatum varied in their sensitivity to hydrogen peroxide. This variation correlated with the amount of catalase in cell-free extracts from the strains. Blastospores and conidiospores of a single isolate were about equally susceptible to hydrogen peroxide, but this sensitivity could obviously vary with the catalase content of the two types of spores. Halides augmented the antifungal activity of hydrogen peroxide for both types of spores. Iodide was far more efficient in this regard than was chloride. A crude granule lysate from guinea pig polymorphonuclear leukocytes was quite inhibitory to blastospore but not to conidiospore germination. A study of the myeloperoxidase activity of such preparations against blastospores was thus precluded. A sample of a very highly purified human myeloperoxidase functioned in the presence of hydrogen peroxide and either iodide or chloride to prevent germination of both blastospores and conidiospores. The preparation had no toxicity for spores apart from its interaction with hydrogen peroxide and halides.
Insights
Histoplasma capsulatum spore sensitivity to hydrogen peroxide varies with catalase levels. Halides, especially iodide, enhance hydrogen peroxide
Area of Science:
- Medical Mycology
- Antimicrobial Mechanisms
- Biochemistry
Background:
- Histoplasma capsulatum is a fungal pathogen causing histoplasmosis.
- Fungal spore resistance is a key factor in infection.
- Understanding spore sensitivity to oxidative stress is crucial for developing treatments.
Purpose of the Study:
- To compare the sensitivity of Histoplasma capsulatum blastospores and conidiospores.
- To investigate the effects of hydrogen peroxide, halides, and myeloperoxidase on spore viability.
- To explore the role of catalase in H. capsulatum's resistance to oxidative stress.
Main Methods:
- Assessing H. capsulatum spore sensitivity to hydrogen peroxide and halides.
- Evaluating the combined effect of myeloperoxidase, hydrogen peroxide, and halides.
- Measuring catalase activity in H. capsulatum extracts.
Main Results:
- Blastospore sensitivity to hydrogen peroxide varied among strains and correlated with catalase content.
- Blastospore and conidiospore susceptibility to hydrogen peroxide was comparable but influenced by catalase.
- Halides, particularly iodide, significantly augmented hydrogen peroxide's antifungal activity.
- Myeloperoxidase in the presence of hydrogen peroxide and halides inhibited germination of both spore types.
Conclusions:
- Catalase levels influence H. capsulatum blastospore resistance to hydrogen peroxide.
- Halide augmentation of hydrogen peroxide activity offers a potential therapeutic strategy.
- Myeloperoxidase plays a role in the oxidative killing of H. capsulatum spores.