Cryptococcus neoformans Can Utilize the Bacterial Melanin Precursor Homogentisic Acid for Fungal Melanogenesis

Abstract

Cryptococcus neoformans melanizes in the environment and in mammalian tissues, but the process of melanization in either venue is mysterious given that this microbe produces melanin only from exogenous substrates. Understanding the process of melanization is important because melanization is believed to protect against various stresses in the environment, including UV radiation, and pigment production is associated with virulence. Melanization in C. neoformans requires the availability of diphenolic precursors. In contrast, many bacteria synthesize melanin from homogentisic acid (HGA). We report that C. neoformans strains representing all four serotypes can produce a brown pigment from HGA. The brown pigment was acid resistant and had the electron paramagnetic resonance spectrum of a stable free radical, qualities that identified it as a melanin. Melanin "ghost"-like particles obtained from pigmented C. neoformans cells were hydrophobic, fluorescent under a variety of irradiation wavelengths, negatively charged, insoluble in organic solvents and alcohols, resistant to degradation by strong acids, and vulnerable to bleaching. HGA melanization was laccase dependent and repressed by high concentrations of glucose. The ability of C. neoformans to utilize a bacterial melanin precursor compound suggests a new substrate source for melanization in the environment.

Galactoxylomannans from Cryptococcus neoformans Varieties neoformans and grubii Are Structurally and Antigenically Variable

“…The x axis represents the diameter size distribution of the GalXM particles measured in nanometers. The y axis corresponds to the percent intensity of weighted sizes (14). Note that there is no panel for GalXM from cap67 grown in minimal medium because we were unable to recover sufficient polysaccharide for this type of analysis in those conditions.…”

The Secreted Pyomelanin Pigment of Legionella pneumophila Confers Ferric Reductase Activity

“…Melanins are also broadly distributed among eukaryotic microorganisms, including fungi and protozoa (70,79 (4,29,33,42,45,55,64,90,102). Among the eukaryotic microbes, endogenous HGA-melanin production is thus far limited to the fungi Aspergillus nidulans and Yarrowia lipolytica (13,36), although it has recently been shown that the fungus Cryptococcus neoformans can use HGA produced by others to achieve melanization (38). Thus, L. pneumophila, along with P. aeruginosa and V. cholerae, is one of the few known producers of HGAmelanin that is also a significant human pathogen.…”

Melanins: Skin Pigments and Much More—Types, Structural Models, Biological Functions, and Formation Routes

“…As these pigments are formed in the brain after infection, a pathogenic neuromelanin is formed using brain compounds [122] and that increases the virulence of the infection. On the other hand, C. neoformans is also able to synthesize pyomelanin derived from a fungal metabolite, homogentisic acid (HGA, Figure 1(h)) [123]. This route gives place to a melanin in the form of "ghost-" like hydrophobic particles, fluorescent under a variety of wavelengths resistant to degradation by strong acids that could increase the virulence of this fungus.…”