Histoplasma capsulatum synthesizes melanin-like pigments in vitro and during mammalian infection

Joshua D. Nosanchuk, Beatriz L. Gómez, Sirida Youngchim, Soraya Díez, Philip Aisen, Rosely M. Zancopé-Oliveira, Angela Restrepo, Arturo Casadevall, Andrew J. Hamilton

Research output: Contribution to journalArticle

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Abstract

Melanin is made by several important pathogenic fungi and has been implicated in the pathogenesis of a number of fungal infections. This study investigated whether the thermally dimorphic fungal pathogen Histoplasma capsulatum var. capsulatum produced melanin or melanin-like compounds in vitro and during infection. Growth of H. capsulatum mycelia in chemically defined minimal medium produced pigmented conidia. Growth of H. capsulatum yeast in chemically defined minimal medium with L-3,4-dihydroxyphenylalanine (DOPA) or (-)epinephrine produced pigmented cells. Treatment of the pigmented cells with proteolytic enzymes, denaturant, and hot concentrated acid yielded dark particles that were similar in size and shape to their respective propagules. Melanin-binding monoclonal antibodies (MAb) labeled pigmented conidia, yeast, and the isolated particles as determined by immunofluorescence microscopy. Electron spin resonance spectroscopy revealed that pigmented yeast cells and particles derived from pigmented cells were stable free radicals consistent with their identification as melanins. Tissues from mice infected with H. capsulatum and from biopsy specimens from a patient with histoplasmosis contained fungal cells that were labeled by melanin-binding MAb. Digestion of infected mouse tissues yielded dark particles that reacted with the melanin-binding MAb and were similar in appearance to H. capsulatum yeast cells. Additionally, sera from infected mice contained antibodies that bound melanin particles. Phenoloxidase activity capable of synthesizing melanin from L-DOPA was detected in cytoplasmic yeast cell extracts. These findings indicate that H. capsulatum conidia and yeast can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may have a similar role to play in the pathogenesis of histoplasmosis.

Original languageEnglish (US)
Pages (from-to)5124-5131
Number of pages8
JournalInfection and Immunity
Volume70
Issue number9
DOIs
StatePublished - Sep 2002

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Histoplasma
Melanins
Infection
Yeasts
Fungal Spores
Histoplasmosis
Monoclonal Antibodies
In Vitro Techniques
Fungi
Dihydroxyphenylalanine
Monophenol Monooxygenase
Mycoses
Mycelium
Electron Spin Resonance Spectroscopy
Levodopa
Virulence Factors
Growth
Cell Extracts
Fluorescence Microscopy
Epinephrine

ASJC Scopus subject areas

  • Immunology

Cite this

Nosanchuk, J. D., Gómez, B. L., Youngchim, S., Díez, S., Aisen, P., Zancopé-Oliveira, R. M., ... Hamilton, A. J. (2002). Histoplasma capsulatum synthesizes melanin-like pigments in vitro and during mammalian infection. Infection and Immunity, 70(9), 5124-5131. https://doi.org/10.1128/IAI.70.9.5124-5131.2002

Histoplasma capsulatum synthesizes melanin-like pigments in vitro and during mammalian infection. / Nosanchuk, Joshua D.; Gómez, Beatriz L.; Youngchim, Sirida; Díez, Soraya; Aisen, Philip; Zancopé-Oliveira, Rosely M.; Restrepo, Angela; Casadevall, Arturo; Hamilton, Andrew J.

In: Infection and Immunity, Vol. 70, No. 9, 09.2002, p. 5124-5131.

Research output: Contribution to journalArticle

Nosanchuk, JD, Gómez, BL, Youngchim, S, Díez, S, Aisen, P, Zancopé-Oliveira, RM, Restrepo, A, Casadevall, A & Hamilton, AJ 2002, 'Histoplasma capsulatum synthesizes melanin-like pigments in vitro and during mammalian infection', Infection and Immunity, vol. 70, no. 9, pp. 5124-5131. https://doi.org/10.1128/IAI.70.9.5124-5131.2002
Nosanchuk, Joshua D. ; Gómez, Beatriz L. ; Youngchim, Sirida ; Díez, Soraya ; Aisen, Philip ; Zancopé-Oliveira, Rosely M. ; Restrepo, Angela ; Casadevall, Arturo ; Hamilton, Andrew J. / Histoplasma capsulatum synthesizes melanin-like pigments in vitro and during mammalian infection. In: Infection and Immunity. 2002 ; Vol. 70, No. 9. pp. 5124-5131.
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