Melanin Remodeling in Budding of Cryptococcus neoformans

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DESCRIPTION (provided by applicant): Cryptococcus neoformans is a pathogenic fungus that is a relatively frequent cause of life-threatening meningitis in patients with impaired immune systems. In addition, C. neoformans is a model organism for the study of pathogenesis and host-pathogen interactions. C. neoformans produces melanin in the presence of appropriate substrate and expression of this pigment is associated with virulence. Several basic aspects of melanin biology in C. neoformans are unknown due to the difficulty is studying it by classical biochemical techniques. Melanin is insoluble and the exact chemical structure of melanin has not been determined. A fundamental question is how do cells break down, or remodel, melanin to allow growth and budding to occur? Melanin degrading enzymes have yet to be identified in any organism but must exist given that the pigment is found in all biological kingdoms. A genetic approach to study melanin remodeling in C. neoformans is proposed. In addition, the importance of melanin remodeling to C. neoformans virulence will be studied.