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.

Factors which control the levels of catalase within yeast cells of Histoplasma capsulatum were studied. Only a small fraction of the total catalase activity could be detected in whole cells. The bulk of the activity was revealed in cell-free extracts or in cells permeabilized with acetone. The formation of the enzyme was regulated by glucose and by oxygen. There were large, consistent differences in the levels of catalase among strains of H. capsulatum. The sensitivity of the strains to H202 toxicity also varied remarkably. Peroxidase activity could not be detected in cell-free extracts of the strains. Resistance to H202 did not correspond to levels of catalase. There was no obvious correlation of H202 sensitivity and virulence among the strains.