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This chapter surveys the available information on Cryptococcus neoformans biochemistry. The C. neoformans capsule is important for virulence and, as a result, the capsular polysaccharide has been studied extensively. Glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoprotein (MP), the three major components of the C. neoformans capsular exopolysaccharides, can each elicit antibody responses, but only the MP component elicits cell-mediated immunity as measured by delayed-type hypersensitivity reaction. The immune response to C. neoformans polysaccharide antigens is discussed. The detection and analysis of capsular polysaccharides in tissue remain dependent upon serological assays. Many assays have been described for the measurement of cryptococcal capsular polysaccharides based on the use of antibody reagents. Electron microscopy of the process of cell wall digestion with snail gut enzymes shows that protoplast-spheroplast formation is a two-stage process. First, the enzymes induce a hole in the equatorial region of the cell wall, through which the protoplast-spheroplast emerges from a cell wall “ ghost”. Second, continued digestion of the cell wall leads to the disappearance of these structures. The biochemistry of melanin and the assembly of melanin on the cell wall remain poorly understood. Melanogenesis is interesting because of its association with virulence and because it is a potential target for antifungal drug design. Mouse passage of environmental C. neoformans isolates produced isolates with higher amphotericin B and fluconazole MICs, suggesting that sterols and antifungal drug resistance could be altered by mammalian infection without a need for exposure to antifungal drugs.
Scanning electron micrograph of encapsulated (top) and nonencapsulated (bottom) C. neoformans strains. On encapsulated strains the capsule appears as a loose fibrillar network (top). For the nonencapsulated strain Cap 67, the surface appears relatively smooth (bottom). Note that bud scars are apparent on some of the nonencapsulated yeast cells. Top micrograph provided by Wendy Cleare (Albert Einstein College of Medicine, Bronx, N.Y.).
Triads identified in GXMs of C. neoformans by proton NMR spectroscopy. Each strain contains a variable amount of each triad (range 0 to 100%). Figure courtesy of Robert Cherniak and reproduced with permission.
Proposed pathway for the oxidation of L-dopa to melanin (reprinted from reference 162 ). Some modifications to this pathway were suggested by Polacheck and Kwon-Chung ( 178 ).
(A) Scanning electron micrograph of melanin ghosts (×15,000). (B) Transmission electron micrograph of a melanin ghost (×45,000). The structure represents melanin left after detergent treatment with guanidinium isothiocyanate and digestion with hot concentrated HCl acid. Reprinted from reference 227 .
Acid phosphatase in C. neoformans cells. Electron-dense deposits inside the cell are due to lead phosphate staining, which indicates the presence of acid phosphatase (×4,500). Note also staining at the edge of the capsule. Figure courtesy of Marta Feldmesser and Phyllis Novikoff (Albert Einstein College of Medicine, Bronx, N.Y.).
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a Based on the factor sera classification of Ikeda et al. ( 88 ).
a Location refers to site of isolation of enzyme or enzyme activity according to the reference cited.
a Adopted from reference 73 . Values are means ± standard deviations. P values are obtained by t-test and adjusted for the Bonferroni correction.

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