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Abstract:
In the presence of hydrogen peroxide and either potassium iodide, sodium chloride, or potassium bromide, purified human myeloperoxidase was rapidly lethal to several species of Candida. Its candidacidal activity was inhibited by cyanide, fluoride, and azide, and by heat inactivation of the enzyme. A hydrogen peroxidegenerating system consisting of d-amino acid oxidase, flavine-adenine dinucleotide, and d-alanine could replace hydrogen peroxide in the candidacidal system. Horseradish peroxidase and human eosinophil granules also exerted candidacidal activity in the presence of iodide and hydrogen peroxide; however, unlike myeloperoxidase or neutrophil granules, these peroxidase sources were inactive when chloride replaced iodide. Cells of Saccharomyces, Geotrichum, and Rhodotorula species, and spores of Aspergillus fumigatus and A. niger were also killed by the combination of myeloperoxidase, iodide, and hydrogen peroxide. Peroxidases, functionally linked to hydrogen peroxide-generating systems, could provide phagocytic cells with the ability to kill many fungal species.
Insights
Human myeloperoxidase (MPO) with hydrogen peroxide and halides effectively kills Candida species. This enzyme system, crucial for phagocytic cells, demonstrates broad antifungal activity against various fungi.
Area of Science:
- Immunology and Microbiology
- Enzymology
Background:
- Phagocytic cells utilize enzymes like myeloperoxidase (MPO) to combat microbial infections.
- The role of MPO in fungal killing, particularly against Candida species, requires further elucidation.
- Understanding the specific conditions and co-factors enhancing MPO's candidacidal activity is essential.
Purpose of the Study:
- To investigate the candidacidal activity of purified human myeloperoxidase (MPO).
- To determine the effect of hydrogen peroxide and various halides (iodide, chloride, bromide) on MPO's antifungal efficacy.
- To explore the potential of alternative hydrogen peroxide-generating systems and other peroxidases in fungal killing.
Main Methods:
- Purified human myeloperoxidase was incubated with hydrogen peroxide and different halide salts (potassium iodide, sodium chloride, potassium bromide).
- Candidacidal activity was assessed against several Candida species.
- Inhibitory effects of cyanide, fluoride, azide, and heat inactivation were tested. Alternative hydrogen peroxide systems and other peroxidases (horseradish peroxidase, eosinophil granules) were also evaluated.
Main Results:
- Human myeloperoxidase demonstrated rapid lethality against multiple Candida species in the presence of hydrogen peroxide and iodide, chloride, or bromide.
- Candidacidal activity was inhibited by cyanide, fluoride, azide, and heat.
- A hydrogen peroxide-generating system (d-amino acid oxidase, flavine-adenine dinucleotide, d-alanine) supported MPO's candidacidal effect. Horseradish peroxidase and eosinophil granules showed activity with iodide but not chloride.
Conclusions:
- Myeloperoxidase, when coupled with hydrogen peroxide and halides, exhibits potent candidacidal activity.
- This enzyme system is effective against a range of fungal species, including Candida, Saccharomyces, Geotrichum, Rhodotorula, Aspergillus fumigatus, and Aspergillus niger.
- Peroxidases linked to hydrogen peroxide-generating systems represent a significant mechanism for phagocytic cells to eliminate fungal pathogens.