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Applied and Environmental Microbiology, January 2007, p. 615-621, Vol. 73, No. 2
0099-2240/07/$08.00+0     doi:10.1128/AEM.01947-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cryptococcus neoformans Can Utilize the Bacterial Melanin Precursor Homogentisic Acid for Fungal Melanogenesis

Susana Frases,^1, Angela Salazar,^1, Ekaterina Dadachova,² and Arturo Casadevall^1,3*

Department of Microbiology and Immunology,¹ Department of Medicine,³ Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, New York 10461²

Received 16 August 2006/ Accepted 2 November 2006

Cryptococcus neoformans melanizes in the environment and in mammalian tissues, but the process of melanization in either venue is mysterious given that this microbe produces melanin only from exogenous substrates. Understanding the process of melanization is important because melanization is believed to protect against various stresses in the environment, including UV radiation, and pigment production is associated with virulence. Melanization in C. neoformans requires the availability of diphenolic precursors. In contrast, many bacteria synthesize melanin from homogentisic acid (HGA). We report that C. neoformans strains representing all four serotypes can produce a brown pigment from HGA. The brown pigment was acid resistant and had the electron paramagnetic resonance spectrum of a stable free radical, qualities that identified it as a melanin. Melanin "ghost"-like particles obtained from pigmented C. neoformans cells were hydrophobic, fluorescent under a variety of irradiation wavelengths, negatively charged, insoluble in organic solvents and alcohols, resistant to degradation by strong acids, and vulnerable to bleaching. HGA melanization was laccase dependent and repressed by high concentrations of glucose. The ability of C. neoformans to utilize a bacterial melanin precursor compound suggests a new substrate source for melanization in the environment.

Published ahead of print on 10 November 2006.

Both authors contributed equally.

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