Blastomyces dermatitidis Produces Melanin In Vitro and During Infection

DAVID VAN DUIN, MD1, PIYALI MANDAL, MSc.2, ARTURO CASADEVALL, MD, PhD2, JOSHUA D. NOSANCHUK, MD2;

Author address: 

1Yale University, New Haven, CT, 2Albert Einstein College of Medicine, Bronx, NY.

Abstract: 

Background: Melanin is made by several important pathogenic fungi and has been implicated in fungal virulence and drug resistance. Methods: Using techniques developed to study melanization in other fungi, we investigated whether Blastomyces dermatitidis (Bd) produces melanin. The effect of melanin on antifungal susceptibility was also assessed. Results: Growth of Bd mycelia in chemically defined minimal media produced pigmented conidia. Growth of Bd yeast in defined media with L-DOPA produced pigmented cells. Treatment of the pigmented cells with proteolytic enzymes, denaturant, and hot concentrated acid yielded dark particles that were similar in size and shape to their respective propagules, consistent with their identification as melanin cell ’ghosts’. Melanin-binding monoclonal antibodies (mAb) bound to pigmented conidia, yeast, and melanin cell ’ghosts’. Electron spin resonance spectroscopy showed that pigmented yeast cells and melanin cell ’ghosts’ contain a population of stable free radicals, a finding consistent with their identification as melanins. Tissues from a dog infected with Bd contained fungal cells that were labeled by melanin-binding mAb. Digestion of the tissues yielded dark particles that reacted with the melanin-binding mAb and were similar in appearance to Bd yeast cells. Melanin has been shown to protect other pathogenic yeast against the activity of certain antifungal compounds and melanization of Bd significantly reduced its susceptibility to amphotericin B, but not to itraconazole or voriconazole. Discussion: These findings indicate that Bd conidia and yeast can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may contribute to the virulence of Bd and melanization may
2004

abstract No: 

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Full conference title: 

42nd Annual Meeting Infectious Diseases Society of America
    • Infectious Diseases Society of America 42nd