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Methods to Inhibit Bacterial Pyomelanin Production and Determine the Corresponding Increase in Sensitivity to Oxidative Stress
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Melanin in Fonsecaea pedrosoi: a trap for oxidative radicals

Marcel M L Cunha1, Anderson J Franzen, Sergio H Seabra

  • 1Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

BMC Microbiology
|March 18, 2010
PubMed
Abstract

Insights

Fonsecaea pedrosoi melanin protects the fungus from macrophage attacks by trapping nitric oxide (NO). Inhibiting melanin production enhances the macrophage oxidative burst, revealing melanin

Area of Science:

  • Mycology
  • Immunology
  • Medical Mycology

Background:

  • Fonsecaea pedrosoi, a pathogenic fungus, produces melanin, a key virulence factor.
  • Melanin in the fungal cell wall offers protection against environmental stressors.
  • Macrophages employ nitric oxide (NO) and oxidative burst to combat fungal infections.

Purpose of the Study:

  • To investigate the role of F. pedrosoi melanin in evading the host immune response, specifically macrophage-mediated oxidative stress.
  • To assess the impact of inhibiting melanin biosynthesis on fungal resistance to NO and macrophage activity.

Main Methods:

  • Macrophages were co-cultured with F. pedrosoi, with or without tricyclazole (TC), an inhibitor of dihydroxynaphthalene (DHN)-melanin synthesis.
  • Nitric oxide (NO) production, macrophage oxidative burst, and inducible nitric oxide synthase (i-NOS) activity were measured.
  • Fungal resistance to H2O2 and a NO donor (SNAP) was evaluated; melanin paramagnetism was analyzed via electron spin resonance.

Main Results:

  • Melanized F. pedrosoi exhibited increased resistance to both H2O2 and NO, with no detectable nitrite in macrophage supernatants.
  • i-NOS expression remained unchanged regardless of fungal treatment, but TC treatment enhanced macrophage oxidative burst.
  • Tricyclazole inhibition of DHN-melanin pathway improved macrophage oxidative burst capability.

Conclusions:

  • F. pedrosoi melanin functions as a potent NO scavenger, enabling fungal escape from macrophage oxidative burst.
  • Melanin's NO-trapping ability is a critical virulence mechanism for F. pedrosoi.
  • Targeting melanin biosynthesis could be a therapeutic strategy to enhance antifungal immunity.

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