Biosynthesis and functions of melanin in Sporothrix schenckii

Sporothrix schenckii is a human pathogen that causes sporotrichosis, an imp ortant cutaneous mycosis with a worldwide distribution. It produces dark-br own conidia, which infect the host, We found that S. schenckii synthesizes melanin via the 1,8-dihydroxynaphthalene pentaketide pathway. Melanin biosy nthesis in the wild type was inhibited by tricyclazole, and colonies of the fungus were reddish brawn instead of black on tricyclazole-amended medium. Two melanin-deficient mutant strains were analyzed in this study: an albin o that produced normal-appearing melanin on scytalone-amended medium and a reddish brown mutant that accumulated and extruded melanin metabolites into its medium, Scytalone and flaviolin obtained from cultures of the reddish brown mutant mere identified by thin-layer chromatography, high-performance liquid chromatography, and UV spectra, Transmission electron microscopy sh owed an electron-dense granular material believed to be melanin in wild-typ e conidial cell malls, and this was absent in conidial walls of the albino mutant unless the albino was grown on a scytalone-amended medium. Melanized cells of wild-type S. schenckii and the albino grown on scytalone-amended medium mere less susceptible to killing by chemically generated oxygen- and nitrogen-derived radicals and by UV light than were conidia of the mutant strains. Melanized conidia of the wild type and the scytalone-treated albin o mere also more resistant to phagocytosis and killing by human monocytes a nd murine macrophages than were unmelanized conidia of the two mutants. The se results demonstrate that melanin protects S. schenckii against certain o xidative antimicrobial compounds and against attack by macrophages.