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6396120 
Journal Article 
Cryptococcus neoformans melanin and virulence: mechanism of action 
Wang, Y; Aisen, P; Casadevall, A 
1995 
Yes 
Infection and Immunity
ISSN: 0019-9567
EISSN: 1098-5522 
63 
8 
3131-3136 
English 
7622240 
Black melanin-like pigments are produced by several neurotropic fungi, including Cryptococcus neoformans. Pigment production is associated with virulence. In media containing phenolic substrates such as L-dopa, C. neoformans cells become black as a result of pigment accumulation. Pigmented and nonpigmented C. neoformans cells were studied with transmission electron microscopy and electron spin resonance (ESR) spectroscopy. Transmission electron microscopy showed electron-dense cell walls, and ESR spectroscopy revealed a stable free-radical population in pigmented cells. The ESR signals of pigmented cells were increased by light, alkaline pH, and Zn2+ and decreased by acid pH, indicating that the black pigment was a type of melanin. A mutant deficient in melanin synthesis (mel) generated by UV radiation lacked ESR-detectable radicals, was less virulent for mice, was more susceptible to killing by nitrogen- and oxygen-derived radicals, and had 100-foldless phenoloxidase activity than the parent strain. The interaction of melanized C. neoformans, nonmelanized C. neoformans, and the hypomelanotic mel mutant with J774.16 murine macrophage-like cells was studied. Melanized cells were more resistant to antibody-mediated phagocytosis and the antifungal effects of murine macrophages than nonmelanized cells. Small increases in the intensity of the ESR signals of melanized cells in solutions containing chemically generated oxygen- and nitrogen-derived radicals indicated electron transfer to or from melanin. Melanin appears to contribute to virulence by protecting fungal cells against attack by immune effector cells. 
; Animals; Base Sequence; Cryptococcus neoformans/chemistry; Cryptococcus neoformans/pathogenicity; DNA Primers/chemistry; Electron Spin Resonance Spectroscopy; Free Radicals; Macrophages/microbiology; Melanins/chemistry; Mice; Mice; Inbred A; Microscopy; Electron; Molecular Sequence Data; Mutagenesis; Nitrogen/chemistry; Phagocytosis; Reactive Oxygen Species/chemistry; Index Medicus/