title: Microstructure of cell wall-associated melanin in the human pathogenic fungus Cryptococcus neoformans.
abstract: Melanin is a virulence factor for many pathogenic fungal species, including Cryptococcus neoformans. Melanin is deposited in the cell wall, and melanin isolated from this fungus retains the shape of the cells, resulting in hollow spheres called "ghosts". In this study, atomic force, scanning electron, and transmission electron microscopy revealed that melanin ghosts are covered with roughly spherical granular particles approximately 40-130 nm in diameter, and that the melanin is arranged in multiple concentric layers. Nuclear magnetic resonance cryoporometry indicated melanin ghosts contain pores with diameters between 1 and 4 nm, in addition to a small number of pores with diameters near 30 nm. Binding of the antibodies to melanin reduced the apparent measured volume of these pores, suggesting a mechanism for their antifungal effect. We propose a model of cryptococcal melanin structure whereby the melanin granules are held together in layers. This structural model has implications for cell division, cell wall remodeling, and antifungal drug discovery.
authors.affiliation: Division of Infectious Diseases of the Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
authors.forename: Helene C
authors.initials: HC
authors.lastname: Eisenman
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
authors.forename: J Beau W
authors.initials: JB
authors.lastname: Webber
authors.forename: Ray J
authors.initials: RJ
authors.lastname: Emerson
authors.forename: Terri A
authors.initials: TA
authors.lastname: Camesano
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000908:Antibodies, Fungal / Q000378:metabolism; D001666:Binding Sites, Antibody; D002473:Cell Wall / Q000737:chemistry / Q000648:ultrastructure; D003455:Cryptococcus neoformans / Q000737:chemistry* / Q000276:immunology / Q000472:pathogenicity* / Q000648:ultrastructure; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008543:Melanins / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D013499:Surface Properties
chemical_list: D000908:Antibodies, Fungal; D008543:Melanins