Melanin in Fonsecaea pedrosoi: a trap for oxidative radicals.
BACKGROUND
The pathogenic fungus Fonsecaea pedrosoi constitutively produces the pigment melanin, an important virulence factor in fungi. Melanin is incorporated in the cell wall structure and provides chemical and physical protection for the fungus.We evaluated the production of nitric oxide (NO) in macrophages, the oxidative burst and the inducible nitric oxide synthase (i-NOS) activity in interactions between activated murine macrophages and F. pedrosoi. Experiments were carried out with or without tricyclazole (TC) treatment, a selective inhibitor of the dihydroxynaphthalene (DHN)-melanin biosynthesis pathway in F. pedrosoi. The paramagnetisms of melanin and the TC-melanin were analysed by electron spin resonance. The fungal growth responses to H2O2 and to S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, were also evaluated.


RESULTS
Melanised F. pedrosoi cells were more resistant to both H2O2 and NO. Nitrite was not detected in the supernatant of macrophages incubated with melanised fungal cells. However, i-NOS expression was unaffected by the presence of either untreated control F. pedrosoi or TC-treated F. pedrosoi. In addition, the inhibition of the DHN-melanin pathway by TC improved the oxidative burst capability of the macrophages.


CONCLUSIONS
The NO-trapping ability of F. pedrosoi melanin is an important mechanism to escape the oxidative burst of macrophages.
Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Marcel M L
MM
Cunha
Anderson J
AJ
Franzen
Sergio H
SH
Seabra
Marcelo H
MH
Herbst
Ney V
NV
Vugman
Luana P
LP
Borba
Wanderley
W
de Souza
Sonia
S
Rozental
D000818:Animals; D001203:Ascomycota / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D008264:Macrophages / Q000166:cytology / Q000382:microbiology; D008543:Melanins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008858:Microscopy, Phase-Contrast; D008872:Microwaves; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D013844:Thiazoles
D005609:Free Radicals; D008543:Melanins; D009573:Nitrites; D013844:Thiazoles; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; C041191:tricyclazole