Melanin in Fonsecaea pedrosoi: a trap for oxidative radicals

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.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.The NO-trapping ability of F. pedrosoi melanin is an important mechanism to escape the oxidative burst of macrophages.Fonsecaea pedrosoi is a soil-borne dimorphic fungus and the major etiological agent of chromoblastomycosis, a chronic disease that can affect immunocompetent hosts. F. pedrosoi is usually limited to skin tissue, most commonly on the lower limbs. 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]. The affected patients are typically low-income workers that engage in agricultural or manual labour in tropical and subtropical countries. Rarely, F. pedrosoi can also cause phaeohyphomycosis, in immunosuppressed patients [3].The management of diseases caused by F. pedrosoi continues to be challenging. Treatment depends on an early diagnosis and the use of systemic antifungal agents and local therapies, includi