Melanin as a potential cryptococcal defence against microbicidal proteins

Cryptococcus neoformans is an important fungal pathogen that synthesizes me lanin when grown in the presence of phenolic substrates. The ability of C. neoformans to produce melanin is associated with virulence, but the specifi c role of melanin in the pathogenesis of infection is not clear. In this st udy the ability of C. neoformans melanin to bind proteins and protect again st microbicidal peptides was investigated. Melanin was shown to bind a vari ety of proteins of fungal and mammalian origin. Melanin-protein interaction s were dependent on the pH of the solution and on the amount of protein and melanin present. Melanized cells were less susceptible to killing by three microbicidal peptides: a defensin, a protegrin, and a magainin. Incubation of the microbicidal peptides with melanin particles, followed by removal o f the melanin, reduced or abolished fungicidal activity, demonstrating inte ractions between peptides and melanin. The ability of melanin to bind prote ins and to protect against microbicidal peptides suggests a protective func tion for melanin, whereby it sequesters microbicidal peptides and abrogates their activity.