Abstract
The opportunistic human pathogenic fungus Aspergillus fumigatus produces at least two types of melanin, namely pyomelanin and dihydroxynaphthalene (DHN) melanin. Pyomelanin is produced during tyrosine catabolism via accumulation of homogentisic acid. Although pyomelanin protects the fungus against reactive oxygen species (ROS) and acts as a defense compound in response to cell wall stress, mutants deficient for pyomelanin biosynthesis do not differ in virulence when tested in a murine infection model for invasive pulmonary aspergillosis. DHN melanin is responsible for the characteristic gray-greenish color of A. fumigatus conidia. Mutants lacking a functional polyketide synthase PksP, the enzyme responsible for the initial step in DHN-melanin formation, i.e., the synthesis of naphthopyrone, produce white spores and are attenuated in virulence. The activity of PksP was found to be essential not only for inhibition of apoptosis of phagocytes by interfering with the host PI3K/Akt signaling cascade but also for effective inhibition of acidification of conidia-containing phagolysosomes. These features allow A. fumigatus to survive in phagocytes and thereby to escape from human immune effector cells and to become a successful pathogen.
Highlights
MELANINS IN FUNGI Among airborne acquired fungal infections of immunocompromised humans, diseases caused by Aspergillus fumigatus clearly predominate (Brakhage, 2005)
This review focus on the two pigments currently known to be produced by A. fumigatus: DHN melanin and pyomelanin
DHN MELANIN AS A VIRULENCE DETERMINANT Pigmentless conidia of A. fumigatus were more effectively killed by macrophages and the pksP mutant was attenuated in virulence in mice infection studies (Jahn et al, 1997, 2000, 2002; Langfelder et al, 1998; Tsai et al, 1998)
Summary
MELANINS IN FUNGI Among airborne acquired fungal infections of immunocompromised humans, diseases caused by Aspergillus fumigatus clearly predominate (Brakhage, 2005). By contrast to pigmentless white conidia, other conidial color mutants of A. fumigatus, that produce yellow, reddish, or brown pigments, show wild-type like ornamentation Transcription of the tyrosine degradation gene cluster was increased under cell wall stress (Jain et al, 2011).
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