MACROPHAGE-MEDIATED AND OXIDANT-MEDIATED INHIBITION OF THE ABILITY OF LIVE BLASTOMYCES-DERMATITIDIS CONIDIA TO TRANSFORM TO THE PATHOGENIC YEAST PHASE - IMPLICATIONS FOR THE PATHOGENESIS OF DIMORPHIC FUNGAL-INFECTIONS

Conidia, produced by the mycelial phase of dimorphic fungi, are thought to represent the infectious form of the organism but must complete a transition to the tissue-invasive, yeast-like phase for infection to ensue. Preventing such transition should effectively eliminate pathogenicity. Using Blastomyces dermatitidis as a target, murine bronchoalveolar macrophages preferentially blocked phase transition after 4 h of incubation with conidia, relatively sparing the ability of conidia to produce hyphae. H2O2, in relatively high concentrations, demonstrated the same activity. The effects of H2O2 seem irreversible, since H2O2-treated conidia that germinated at 48 h at 25-degrees-C were still unable to produce yeasts over the next 5 days when incubated at 37-degrees-C. Catalase idative defense mechanisms may be operative in vivo. Since conidia do not form mycelia at temperatures found in mammalian hosts, these effects may represent a novel host defense mechanism against dimorphic fungal pathogens.