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.

Studies on the catalase of Histoplasma capsulatum

“…phages exposed to lymphocytes from animals recovering from sublethal infections (16). For some time I have examined likely mechanisms for the modification of intracellular growth within mouse macrophages (13)(14)(15). Although oxidative antifungal systems are clearly operative in neutrophils (11,15), they probably are less important in the antimicrobial armamentarium of the mature macrophage (14).…”

“…For some time I have examined likely mechanisms for the modification of intracellular growth within mouse macrophages (13)(14)(15). Although oxidative antifungal systems are clearly operative in neutrophils (11,15), they probably are less important in the antimicrobial armamentarium of the mature macrophage (14). Nevertheless, H202 is generated by mouse macrophages stimulated in certain ways (4,26,27), and this product of the oxidative burst is thought to play an important role in killing Mycobacterium tuberculosis (18,19).…”

“…The viability of the cells after exposure to H202 was tested by assessment of cell germination (15). One loopful of the reaction mixtures was placed on blocks of GPA (15). The number of germlings was determined after 24 and 48 h of incubation at 30°C.…”

“…The most extensively examined of the antifungal properties of polymorphonuclear neutrophils is the oxidative system involving H202, a halide, and the enzyme myeloperoxidase. This system efficiently kills both conidiospores and yeast cells of H. capsulatum (13)(14)(15).…”

“…The preliminary assays necessary to a study of the myeloperoxidase system revealed a remarkable disparity of sensitivity to H202 toxicity among strains of H. capsulatum (15). Initially, three isolates were examined, and among them there was a correlation of H202 sensitivity with catalase levels in the cells (15). Examination of a larger number of strains proved that the three isolates originally chosen were not repre-…”