Melanin as a potential cryptococcal defence against microbicidal proteins.
Cryptococcus neoformans is an important fungal pathogen that synthesizes melanin when grown in the presence of phenolic substrates. The ability of C. neoformans to produce melanin is associated with virulence, but the specific role of melanin in the pathogenesis of infection is not clear. In this study the ability of C. neoformans melanin to bind proteins and protect against microbicidal peptides was investigated. Melanin was shown to bind a variety of proteins of fungal and mammalian origin. Melanin-protein interactions 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 of the melanin, reduced or abolished fungicidal activity, demonstrating interactions between peptides and melanin. The ability of melanin to bind proteins and to protect against microbicidal peptides suggests a protective function for melanin, whereby it sequesters microbicidal peptides and abrogates their activity.
The Department of Pharmacology, Cornell University Medical College, New York, NY 10021, USA. tdoering@mail.med.cornell.edu
T L
TL
Doering
J D
JD
Nosanchuk
W K
WK
Roberts
A
A
Casadevall
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000378:metabolism*; D003455:Cryptococcus neoformans / Q000378:metabolism*; D023082:Defensins; D005656:Fungal Proteins / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012996:Solutions
D000935:Antifungal Agents; D023082:Defensins; D005656:Fungal Proteins; D008543:Melanins; D010455:Peptides; D011506:Proteins; D012996:Solutions