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Cryptococcus neoformans melanization incorporates multiple catecholamines to produce polytypic melanin

Melanin is a major virulence factor in pathogenic fungi that enhances the ability of fungal cells to resist immune clearance. Cryptococcus neoformans is an important human pathogenic fungus that synthesizes melanin from exogenous tissue catecholamine precursors during infection, but the type of mela...

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Autores principales: Baker, Rosanna P., Chrissian, Christine, Stark, Ruth E., Casadevall, Arturo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760516/
https://www.ncbi.nlm.nih.gov/pubmed/34942148
http://dx.doi.org/10.1016/j.jbc.2021.101519
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author Baker, Rosanna P.
Chrissian, Christine
Stark, Ruth E.
Casadevall, Arturo
author_facet Baker, Rosanna P.
Chrissian, Christine
Stark, Ruth E.
Casadevall, Arturo
author_sort Baker, Rosanna P.
collection PubMed
description Melanin is a major virulence factor in pathogenic fungi that enhances the ability of fungal cells to resist immune clearance. Cryptococcus neoformans is an important human pathogenic fungus that synthesizes melanin from exogenous tissue catecholamine precursors during infection, but the type of melanin made in cryptococcal meningoencephalitis is unknown. We analyzed the efficacy of various catecholamines found in brain tissue in supporting melanization using animal brain tissue and synthetic catecholamine mixtures reflecting brain tissue proportions. Solid-state NMR spectra of the melanin pigment produced from such mixtures yielded more melanin than expected if only the preferred constituent dopamine had been incorporated, suggesting uptake of additional catecholamines. Probing the biosynthesis of melanin using radiolabeled catecholamines revealed that C. neoformans melanization simultaneously incorporated more than one catecholamine, implying that the pigment was polytypic in nature. Nonetheless, melanin derived from individual or mixed catecholamines had comparable ability to protect C. neoformans against ultraviolet light and oxidants. Our results indicate that melanin produced during infection differs depending on the catecholamine composition of tissue and that melanin pigment synthesized in vivo is likely to accrue from the polymerization of a mixture of precursors. From a practical standpoint, our results strongly suggest that using dopamine as a polymerization precursor is capable of producing melanin pigment comparable to that produced during infection. On a more fundamental level, our findings uncover additional structural complexity for natural cryptococcal melanin by demonstrating that pigment produced during human infection is likely to be composed of polymerized moieties derived from chemically different precursors.
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spelling pubmed-87605162022-01-19 Cryptococcus neoformans melanization incorporates multiple catecholamines to produce polytypic melanin Baker, Rosanna P. Chrissian, Christine Stark, Ruth E. Casadevall, Arturo J Biol Chem Research Article Melanin is a major virulence factor in pathogenic fungi that enhances the ability of fungal cells to resist immune clearance. Cryptococcus neoformans is an important human pathogenic fungus that synthesizes melanin from exogenous tissue catecholamine precursors during infection, but the type of melanin made in cryptococcal meningoencephalitis is unknown. We analyzed the efficacy of various catecholamines found in brain tissue in supporting melanization using animal brain tissue and synthetic catecholamine mixtures reflecting brain tissue proportions. Solid-state NMR spectra of the melanin pigment produced from such mixtures yielded more melanin than expected if only the preferred constituent dopamine had been incorporated, suggesting uptake of additional catecholamines. Probing the biosynthesis of melanin using radiolabeled catecholamines revealed that C. neoformans melanization simultaneously incorporated more than one catecholamine, implying that the pigment was polytypic in nature. Nonetheless, melanin derived from individual or mixed catecholamines had comparable ability to protect C. neoformans against ultraviolet light and oxidants. Our results indicate that melanin produced during infection differs depending on the catecholamine composition of tissue and that melanin pigment synthesized in vivo is likely to accrue from the polymerization of a mixture of precursors. From a practical standpoint, our results strongly suggest that using dopamine as a polymerization precursor is capable of producing melanin pigment comparable to that produced during infection. On a more fundamental level, our findings uncover additional structural complexity for natural cryptococcal melanin by demonstrating that pigment produced during human infection is likely to be composed of polymerized moieties derived from chemically different precursors. American Society for Biochemistry and Molecular Biology 2021-12-20 /pmc/articles/PMC8760516/ /pubmed/34942148 http://dx.doi.org/10.1016/j.jbc.2021.101519 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Baker, Rosanna P.
Chrissian, Christine
Stark, Ruth E.
Casadevall, Arturo
Cryptococcus neoformans melanization incorporates multiple catecholamines to produce polytypic melanin
title Cryptococcus neoformans melanization incorporates multiple catecholamines to produce polytypic melanin
title_full Cryptococcus neoformans melanization incorporates multiple catecholamines to produce polytypic melanin
title_fullStr Cryptococcus neoformans melanization incorporates multiple catecholamines to produce polytypic melanin
title_full_unstemmed Cryptococcus neoformans melanization incorporates multiple catecholamines to produce polytypic melanin
title_short Cryptococcus neoformans melanization incorporates multiple catecholamines to produce polytypic melanin
title_sort cryptococcus neoformans melanization incorporates multiple catecholamines to produce polytypic melanin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760516/
https://www.ncbi.nlm.nih.gov/pubmed/34942148
http://dx.doi.org/10.1016/j.jbc.2021.101519
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