Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/33095
Type
ArticleCopyright
Open access
Embargo date
2020-05-15
Collections
- INI - Artigos de Periódicos [3488]
Metadata
Show full item record
HISTOPLASMA CAPSULATUM SYNTHESIZES MELANIN-LIKE PIGMENTS IN VITRO AND DURING MAMMALIAN INFECTION
Author
Affilliation
Albert Einstein College of Medicine. Department of Medicine. New York, NY, USA.
Guy’s, Kings, and St. Thomas Medical Schools.Guy’s Hospital. St. Johns Institute of Dermatology. Dermatology Department. London, UK / Corporación para Investigaciones Biológicas. Medellín, Colombia.
Guy’s, Kings, and St. Thomas Medical Schools.Guy’s Hospital. St. Johns. Institute of Dermatology. Dermatology Department. London, UK / Chiang-Mai Medical School. Microbiology Department. Chiang-Mai, Thailand.
Guy’s, Kings, and St. Thomas Medical Schools.Guy’s Hospital. St. Johns Institute of Dermatology. Dermatology Department. London, UK / Corporación para Investigaciones Biológicas. Medellín, Colombia.
Albert Einstein College of Medicine. Department of Physiology and Biophysics. New York, NY, USA.
Fundação Oswaldo Cruz. Centro de Pesquisas Hospital Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Corporación para Investigaciones Biológicas. Medellín, Colombia.
Albert Einstein College of Medicine. Department of Medicine. New York, NY, USA / Albert Einstein College of Medicine. Department of Microbiology and Immunology. New York, NY, USA.
Guy’s, Kings, and St. Thomas Medical Schools.Guy’s Hospital. St. Johns. Institute of Dermatology. Dermatology Department. London, UK.
Guy’s, Kings, and St. Thomas Medical Schools.Guy’s Hospital. St. Johns Institute of Dermatology. Dermatology Department. London, UK / Corporación para Investigaciones Biológicas. Medellín, Colombia.
Guy’s, Kings, and St. Thomas Medical Schools.Guy’s Hospital. St. Johns. Institute of Dermatology. Dermatology Department. London, UK / Chiang-Mai Medical School. Microbiology Department. Chiang-Mai, Thailand.
Guy’s, Kings, and St. Thomas Medical Schools.Guy’s Hospital. St. Johns Institute of Dermatology. Dermatology Department. London, UK / Corporación para Investigaciones Biológicas. Medellín, Colombia.
Albert Einstein College of Medicine. Department of Physiology and Biophysics. New York, NY, USA.
Fundação Oswaldo Cruz. Centro de Pesquisas Hospital Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Corporación para Investigaciones Biológicas. Medellín, Colombia.
Albert Einstein College of Medicine. Department of Medicine. New York, NY, USA / Albert Einstein College of Medicine. Department of Microbiology and Immunology. New York, NY, USA.
Guy’s, Kings, and St. Thomas Medical Schools.Guy’s Hospital. St. Johns. Institute of Dermatology. Dermatology Department. London, UK.
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 melaninbinding 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.
Share