Catecholamine Oxidative Products, but Not Melanin, Are Produced by Cryptococcus neoformans during Neuropathogenesis in Mice

L Liu, K Wakamatsu, S Ito, PR Williamson - Infection and immunity, 1999 - Am Soc Microbiol
L Liu, K Wakamatsu, S Ito, PR Williamson
Infection and immunity, 1999Am Soc Microbiol
Melanin has been proposed as a virulence factor in Cryptococcus neoformans, but its
presence has not been shown unambiguously in vivo. Validated methods used previously to
show production of cryptococcal eumelanin pigment in vitro (PR Williamson, K. Wakamatsu,
and S. Ito, J. Bacteriol. 180: 1570–1572, 1998) were used to assess for production of
laccase-derived products in mouse brain of the Lacc+ strains, 2E-TUC, H99 (serotype A),
and ATCC 34873 (serotype D), and the Lacc− strain, 2E-TU. Pyrrole-2, 3, 5-tricarboxylic and …
Abstract
Melanin has been proposed as a virulence factor inCryptococcus neoformans, but its presence has not been shown unambiguously in vivo. Validated methods used previously to show production of cryptococcal eumelanin pigment in vitro (P. R. Williamson, K. Wakamatsu, and S. Ito, J. Bacteriol. 180:1570–1572, 1998) were used to assess for production of laccase-derived products in mouse brain of the Lacc+ strains, 2E-TUC, H99 (serotype A), and ATCC 34873 (serotype D), and the Lacc strain, 2E-TU. Pyrrole-2,3,5-tricarboxylic and pyrrole-2,3-dicarboxylic acid, specific degradation products of catecholamine derivatives such as melanin, were found in all Lacc+ strains, but not in the Lacc strain, 2E-TU. However, the presence of melanin pigment itself could not be demonstrated in the same cells. Lack of the specific degradation products aminohydroxyphenylalanine and aminohydroxyphenylethylamine in Lacc+ strains upon hydriodic acid hydrolysis showed that pheomelanin was also not produced by the fungus in vivo. These are the first data to support the generation of catecholamine oxidation products by C. neoformans in vivo, but they do not support postenzymatic polymerization of these products to form typical eumelanin, as previously proposed.
American Society for Microbiology