Melanin in the dimorphic fungal pathogen Paracoccidioides brasiliensis: effects on phagocytosis, intracellular resistance and drug susceptibility

Melanin in the dimorphic fungal pathogen Paracoccidioides brasiliensis: effects on phagocytosis, intracellular resistance and drug susceptibility

Author Silva, M. B. da Google Scholar
Marques, A. F. Google Scholar
Nosanchuk, J. D. Google Scholar
Casadevall, A. Google Scholar
Travassos, L. R. Google Scholar
Taborda, Carlos Pelleschi Autor UNIFESP Google Scholar
Institution Universidade de São Paulo (USP)
Albert Einstein Coll Med
Universidade Federal de São Paulo (UNIFESP)
Abstract The fungal pathogen Paracoccidioides brasiliensis produces a melanin-like pigment in the presence of L-DOPA in vitro. We investigated whether melanization affected yeast uptake by alveolar and peritoneal macrophages, the intracellular resistance of fungal cells and their susceptibility to antifungal drugs. the interactions of melanized and nonmelanized P brasiliensis with murine primary macrophages and J774.16 and MH-S macrophage-like cell lines were investigated. Melanized yeast cells were poorly phagocytosed by the cells even in the presence of complement. Melanization caused significant interference with the binding of cell wall components to lectin receptors on macrophages. Melanized cells were also more resistant than nonmelanized cells to the antifungal activity of murine macrophages. No difference in the susceptibilities of melanized and nonmelanized P brasiliensis to antifungal drugs was observed using the minimum inhibitory concentration (MIC) method. However killing assays showed that melanization significantly reduced fungal susceptibility to amphotericin B and also protected against ketoconazole, fluconazole, itraconazole and sulfarnethoxazole. the present results indicate that fungal melanin protects P. brasiliensis from phagocytosis and increases its resistance to antifungal drugs. (c) 2005 Elsevier SAS. All rights reserved.
Keywords Paracoccidioides brasiliensis
melanin
phagocytosis
resistance
Language English
Date 2006-01-01
Published in Microbes and Infection. Amsterdam: Elsevier B.V., v. 8, n. 1, p. 197-205, 2006.
ISSN 1286-4579 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 197-205
Origin http://dx.doi.org/10.1016/j.micinf.2005.06.018
Access rights Closed access
Type Article
Web of Science ID WOS:000235441700023
URI http://repositorio.unifesp.br/handle/11600/28650

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