Cryptococcus neoformans is a fungus that is pathogenic in humans and that c
an produce melanin in vitro. Melanization is associated with virulence, but
there is no evidence that melanin is made during infection. Melanins are d
ifficult to study because they are amorphous and insoluble. Melanin-binding
peptides from a phage display library were used to demonstrate that C. neo
formans makes melanin-like compounds in tissue. Melanin-binding peptides we
re characterized by a high proportion of positively charged and aromatic re
sidues. Two other methods, demonstration of an antibody response to melanin
in mice infected with C. neoformans and analysis of yeast cell walls in in
fected tissue by light microscopy, were used to support these findings. The
demonstration that C. neoformans melanizes in tissue has important implica
tions for pathogenesis and drug discovery.