Melanin in Fonsecaea pedrosoi: a trap for oxidative radicals

Marcel Ml Cunha,Luana P Borba,Marcelo H Herbst,Wanderley De Souza,Ney V Vugman,Sergio H Seabra,Sonia Rozental,Anderson J Franzen

doi:10.1186/1471-2180-10-80

Abstract

BackgroundThe 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.ResultsMelanised 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.ConclusionThe NO-trapping ability of F. pedrosoi melanin is an important mechanism to escape the oxidative burst of macrophages.

Highlights

The pathogenic fungus Fonsecaea pedrosoi constitutively produces the pigment melanin, an important virulence factor in fungi
I-NOS expression was unaffected by the presence of either untreated control F. pedrosoi or TC-treated F. pedrosoi
Formazan precipitation was observed near S. cerevisiae (Fig. 2D) and F. pedrosoi grown in melanin-deficient conditions, such as with TC treatment (Fig. 2A) or low aeration (Fig. 2B)

Summary

Introduction

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. Experiments were carried out with or without tricyclazole (TC) treatment, a selective inhibitor of the dihydroxynaphthalene (DHN)melanin biosynthesis pathway in F. pedrosoi. Fonsecaea pedrosoi is a soil-borne dimorphic fungus and the major etiological agent of chromoblastomycosis, a chronic disease that can affect immunocompetent hosts. Infection usually occurs after exposure to the fungus via contaminated soil, splinters or sharp farm equipment, and results in long-term inflammation, suppurative granulomatous dermatitis and fibrosis [1,2]. F. pedrosoi can cause phaeohyphomycosis, in immunosuppressed patients [3]. The management of diseases caused by F. pedrosoi continues to be challenging. Relapses are common [4,5]

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