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

Marcelo B. Da Silva, Alexandre F. Marques, Joshua D. Nosanchuk, Arturo Casadevall, Luiz R. Travassos, Carlos P. Taborda

Research output: Contribution to journalArticle

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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 sulfamethoxazole. The present results indicate that fungal melanin protects P. brasiliensis from phagocytosis and increases its resistance to antifungal drugs.

Original languageEnglish (US)
Pages (from-to)197-205
Number of pages9
JournalMicrobes and Infection
Volume8
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Paracoccidioides
Melanins
Phagocytosis
Drug Resistance
Macrophages
Fungal Drug Resistance
Yeasts
Mitogen Receptors
Sulfamethoxazole
Cytophagocytosis
Ketoconazole
Itraconazole
Fluconazole
Alveolar Macrophages
Peritoneal Macrophages
Microbial Sensitivity Tests
Amphotericin B
Cellular Structures
Pharmaceutical Preparations
Cell Wall

Keywords

  • Melanin
  • Paracoccidioides brasiliensis
  • Phagocytosis
  • Resistance

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this

Melanin in the dimorphic fungal pathogen Paracoccidioides brasiliensis : Effects on phagocytosis, intracellular resistance and drug susceptibility. / Da Silva, Marcelo B.; Marques, Alexandre F.; Nosanchuk, Joshua D.; Casadevall, Arturo; Travassos, Luiz R.; Taborda, Carlos P.

In: Microbes and Infection, Vol. 8, No. 1, 01.2006, p. 197-205.

Research output: Contribution to journalArticle

Da Silva, Marcelo B. ; Marques, Alexandre F. ; Nosanchuk, Joshua D. ; Casadevall, Arturo ; Travassos, Luiz R. ; Taborda, Carlos P. / Melanin in the dimorphic fungal pathogen Paracoccidioides brasiliensis : Effects on phagocytosis, intracellular resistance and drug susceptibility. In: Microbes and Infection. 2006 ; Vol. 8, No. 1. pp. 197-205.
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