Mechanisms of Resistance in the Systemic Mycoses

Howard, Dexter H.

doi:10.1007/978-1-4684-1009-9_19

Cited by 10 publications

(6 citation statements)

References 194 publications

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“…The overall goal of work in my laboratory is to understand the intracellular behavior of the fungus within macrophages. Mouse macrophages in cell culture can be used to derive some information about the intracellular behavior of the fungus (12,14). The growth of the fungus is suppressed within normal macro-1164 HOWARD a Catalase activity is recorded in milliequivalents of H202 destroyed per milligram (dry weight) of cells per minute.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

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confidence: 99%

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Studies on the catalase of Histoplasma capsulatum

Howard¹

1983

Infect Immun

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Studies on the catalase of Histoplasma capsulatum

Howard¹

1983

Infect Immun

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“…Previously I have reported on the sensitivity of blastospores of H. capsulatum to the myeloperoxidase system (10)(11)(12). The interaction of zoopathogenic fungi and phagocytic cells and cellular mechanisms mediating antifungal effects has been reviewed recently (13). In this paper I will describe results from experiments on the comparative sensitivity of conidiospores and blastospores to that oxidative system.…”

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confidence: 99%

Comparative sensitivity of Histoplasma capsulatum conidiospores and blastospores to oxidative antifungal systems

Howard¹

1981

Infect Immun

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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.

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