Macrophage- 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 in-fectious 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 pathogenic-ity. Using Blastomyces dermatitidis as a target, murine bronchoalveolar macrophages preferen-tially blocked phase transition after 4 h of incubation with conidia, relatively sparing the ability of conidia to produce hyphae. H202, in relatively high concentrations, demonstrated the same activity. The effects of H202seem irreversible, since H202-treated conidia that germinated at 48 h at 25°C were still unable to produce yeasts over the next 5 days when incubated at 37°C. Catalase could not reverse the macrophage-induced inhibition of phase transition, suggesting that nonox-idative defense mechanisms may beoperative in vivo. Since conidia do not form mycelia at tem-peratures found in mammalian hosts, these effects may represent a novel host defense mechanism against dimorphic fungal pathogens. Blastomyces dermatitidisis a dimorphic fungus that causes blastomycosis. Conidia, produced by specialized mycelial structures, conidiophores, represent the infectious particle [1