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Melanization of Candida auris Is Associated with Alteration of Extracellular pH

Candida auris is a recently emerged global fungal pathogen, which causes life-threatening infections, often in healthcare settings. C. auris infections are worrisome because the fungus is often resistant to multiple antifungal drug classes. Furthermore, C. auris forms durable and difficult to remove...

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Autores principales: Smith, Daniel F. Q., Mudrak, Nathan J., Zamith-Miranda, Daniel, Honorato, Leandro, Nimrichter, Leonardo, Chrissian, Christine, Smith, Barbara, Gerfen, Gary, Stark, Ruth E., Nosanchuk, Joshua D., Casadevall, Arturo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604884/
https://www.ncbi.nlm.nih.gov/pubmed/36294632
http://dx.doi.org/10.3390/jof8101068
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author Smith, Daniel F. Q.
Mudrak, Nathan J.
Zamith-Miranda, Daniel
Honorato, Leandro
Nimrichter, Leonardo
Chrissian, Christine
Smith, Barbara
Gerfen, Gary
Stark, Ruth E.
Nosanchuk, Joshua D.
Casadevall, Arturo
author_facet Smith, Daniel F. Q.
Mudrak, Nathan J.
Zamith-Miranda, Daniel
Honorato, Leandro
Nimrichter, Leonardo
Chrissian, Christine
Smith, Barbara
Gerfen, Gary
Stark, Ruth E.
Nosanchuk, Joshua D.
Casadevall, Arturo
author_sort Smith, Daniel F. Q.
collection PubMed
description Candida auris is a recently emerged global fungal pathogen, which causes life-threatening infections, often in healthcare settings. C. auris infections are worrisome because the fungus is often resistant to multiple antifungal drug classes. Furthermore, C. auris forms durable and difficult to remove biofilms. Due to the relatively recent, resilient, and resistant nature of C. auris, we investigated whether it produces the common fungal virulence factor melanin. Melanin is a black-brown pigment typically produced following enzymatic oxidation of aromatic precursors, which promotes fungal virulence through oxidative stress resistance, mammalian immune response evasion, and antifungal peptide and pharmaceutical inactivation. We found that certain strains of C. auris oxidized L-DOPA and catecholamines into melanin. Melanization occurred extracellularly in a process mediated by alkalinization of the extracellular environment, resulting in granule-like structures that adhere to the fungus’ external surface. C. auris had relatively high cell surface hydrophobicity, but there was no correlation between hydrophobicity and melanization. Melanin protected the fungus from oxidative damage, but we did not observe a protective role during infection of macrophages or Galleria mellonella larvae. In summary, C. auris alkalinizes the extracellular medium, which promotes the non-enzymatic oxidation of L-DOPA to melanin that attaches to its surface, thus illustrating a novel mechanism for fungal melanization.
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spelling pubmed-96048842022-10-27 Melanization of Candida auris Is Associated with Alteration of Extracellular pH Smith, Daniel F. Q. Mudrak, Nathan J. Zamith-Miranda, Daniel Honorato, Leandro Nimrichter, Leonardo Chrissian, Christine Smith, Barbara Gerfen, Gary Stark, Ruth E. Nosanchuk, Joshua D. Casadevall, Arturo J Fungi (Basel) Article Candida auris is a recently emerged global fungal pathogen, which causes life-threatening infections, often in healthcare settings. C. auris infections are worrisome because the fungus is often resistant to multiple antifungal drug classes. Furthermore, C. auris forms durable and difficult to remove biofilms. Due to the relatively recent, resilient, and resistant nature of C. auris, we investigated whether it produces the common fungal virulence factor melanin. Melanin is a black-brown pigment typically produced following enzymatic oxidation of aromatic precursors, which promotes fungal virulence through oxidative stress resistance, mammalian immune response evasion, and antifungal peptide and pharmaceutical inactivation. We found that certain strains of C. auris oxidized L-DOPA and catecholamines into melanin. Melanization occurred extracellularly in a process mediated by alkalinization of the extracellular environment, resulting in granule-like structures that adhere to the fungus’ external surface. C. auris had relatively high cell surface hydrophobicity, but there was no correlation between hydrophobicity and melanization. Melanin protected the fungus from oxidative damage, but we did not observe a protective role during infection of macrophages or Galleria mellonella larvae. In summary, C. auris alkalinizes the extracellular medium, which promotes the non-enzymatic oxidation of L-DOPA to melanin that attaches to its surface, thus illustrating a novel mechanism for fungal melanization. MDPI 2022-10-11 /pmc/articles/PMC9604884/ /pubmed/36294632 http://dx.doi.org/10.3390/jof8101068 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Smith, Daniel F. Q.
Mudrak, Nathan J.
Zamith-Miranda, Daniel
Honorato, Leandro
Nimrichter, Leonardo
Chrissian, Christine
Smith, Barbara
Gerfen, Gary
Stark, Ruth E.
Nosanchuk, Joshua D.
Casadevall, Arturo
Melanization of Candida auris Is Associated with Alteration of Extracellular pH
title Melanization of Candida auris Is Associated with Alteration of Extracellular pH
title_full Melanization of Candida auris Is Associated with Alteration of Extracellular pH
title_fullStr Melanization of Candida auris Is Associated with Alteration of Extracellular pH
title_full_unstemmed Melanization of Candida auris Is Associated with Alteration of Extracellular pH
title_short Melanization of Candida auris Is Associated with Alteration of Extracellular pH
title_sort melanization of candida auris is associated with alteration of extracellular ph
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604884/
https://www.ncbi.nlm.nih.gov/pubmed/36294632
http://dx.doi.org/10.3390/jof8101068
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