Laccase Affects the Rate of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Nonlytic Exocytosis from Macrophages

ABSTRACT Nonlytic exocytosis is a process in which previously ingested microbes are expelled from host phagocytes with the concomitant survival of both cell types. This process has been observed in the interaction of Cryptococcus spp. and other fungal cells with phagocytes as distant as mammalian, b...

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Autores principales:	Stefânia de Oliveira Frazão, Herdson Renney de Sousa, Lenise Gonçalves da Silva, Jéssica dos Santos Folha, Kaio César de Melo Gorgonha, Getúlio Pereira de Oliveira, Maria Sueli Soares Felipe, Ildinete Silva-Pereira, Arturo Casadevall, André Moraes Nicola, Patrícia Albuquerque
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Cryptococcus neoformans laccase macrophages nonlytic exocytosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/30eb6029a2d44935b1d01fe5154fca5a
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spelling	oai:doaj.org-article:30eb6029a2d44935b1d01fe5154fca5a2021-11-15T16:19:09ZLaccase Affects the Rate of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Nonlytic Exocytosis from Macrophages10.1128/mBio.02085-202150-7511https://doaj.org/article/30eb6029a2d44935b1d01fe5154fca5a2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02085-20https://doaj.org/toc/2150-7511ABSTRACT Nonlytic exocytosis is a process in which previously ingested microbes are expelled from host phagocytes with the concomitant survival of both cell types. This process has been observed in the interaction of Cryptococcus spp. and other fungal cells with phagocytes as distant as mammalian, bird, and fish macrophages and ameboid predators. Despite a great amount of research dedicated to unraveling this process, there are still many questions about its regulation and its final benefits for host or fungal cells. During a study to characterize the virulence attributes of Brazilian clinical isolates of C. neoformans, we observed great variability in their rates of nonlytic exocytosis and noted a correlation between this process and fungal melanin production/laccase activity. Flow cytometry experiments using melanized cells, nonmelanized cells, and lac1Δ mutants revealed that laccase has a role in the process of nonlytic exocytosis that seems to be independent of melanin production. These results identify a role for laccase in virulence, independent of its role in pigment production, that represents a new variable in the regulation of nonlytic exocytosis. IMPORTANCE Cryptococcus neoformans is a yeast that causes severe disease, primarily in immunosuppressed people. It has many attributes that allow it to survive and cause disease, such as a polysaccharide capsule and the dark pigment melanin produced by the laccase enzyme. Upon infection, the yeast is ingested by cells called macrophages, whose function is to kill them. Instead, these fungal cells can exit from macrophages in a process called nonlytic exocytosis. We know that this process is controlled by both host and fungal factors, only some of which are known. As part of an ongoing study, we observed that C. neoformans isolates that produce melanin faster are more-frequent targets of nonlytic exocytosis. Further experiments showed that this is probably due to higher production of laccase, because fungi lacking this enzyme are nonlytically exocytosed less often. This shows that laccase is an important signal/regulator of nonlytic exocytosis of C. neoformans from macrophages.Stefânia de Oliveira FrazãoHerdson Renney de SousaLenise Gonçalves da SilvaJéssica dos Santos FolhaKaio César de Melo GorgonhaGetúlio Pereira de OliveiraMaria Sueli Soares FelipeIldinete Silva-PereiraArturo CasadevallAndré Moraes NicolaPatrícia AlbuquerqueAmerican Society for MicrobiologyarticleCryptococcus neoformanslaccasemacrophagesnonlytic exocytosisMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cryptococcus neoformans laccase macrophages nonlytic exocytosis Microbiology QR1-502
spellingShingle	Cryptococcus neoformans laccase macrophages nonlytic exocytosis Microbiology QR1-502 Stefânia de Oliveira Frazão Herdson Renney de Sousa Lenise Gonçalves da Silva Jéssica dos Santos Folha Kaio César de Melo Gorgonha Getúlio Pereira de Oliveira Maria Sueli Soares Felipe Ildinete Silva-Pereira Arturo Casadevall André Moraes Nicola Patrícia Albuquerque Laccase Affects the Rate of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Nonlytic Exocytosis from Macrophages
description	ABSTRACT Nonlytic exocytosis is a process in which previously ingested microbes are expelled from host phagocytes with the concomitant survival of both cell types. This process has been observed in the interaction of Cryptococcus spp. and other fungal cells with phagocytes as distant as mammalian, bird, and fish macrophages and ameboid predators. Despite a great amount of research dedicated to unraveling this process, there are still many questions about its regulation and its final benefits for host or fungal cells. During a study to characterize the virulence attributes of Brazilian clinical isolates of C. neoformans, we observed great variability in their rates of nonlytic exocytosis and noted a correlation between this process and fungal melanin production/laccase activity. Flow cytometry experiments using melanized cells, nonmelanized cells, and lac1Δ mutants revealed that laccase has a role in the process of nonlytic exocytosis that seems to be independent of melanin production. These results identify a role for laccase in virulence, independent of its role in pigment production, that represents a new variable in the regulation of nonlytic exocytosis. IMPORTANCE Cryptococcus neoformans is a yeast that causes severe disease, primarily in immunosuppressed people. It has many attributes that allow it to survive and cause disease, such as a polysaccharide capsule and the dark pigment melanin produced by the laccase enzyme. Upon infection, the yeast is ingested by cells called macrophages, whose function is to kill them. Instead, these fungal cells can exit from macrophages in a process called nonlytic exocytosis. We know that this process is controlled by both host and fungal factors, only some of which are known. As part of an ongoing study, we observed that C. neoformans isolates that produce melanin faster are more-frequent targets of nonlytic exocytosis. Further experiments showed that this is probably due to higher production of laccase, because fungi lacking this enzyme are nonlytically exocytosed less often. This shows that laccase is an important signal/regulator of nonlytic exocytosis of C. neoformans from macrophages.
format	article
author	Stefânia de Oliveira Frazão Herdson Renney de Sousa Lenise Gonçalves da Silva Jéssica dos Santos Folha Kaio César de Melo Gorgonha Getúlio Pereira de Oliveira Maria Sueli Soares Felipe Ildinete Silva-Pereira Arturo Casadevall André Moraes Nicola Patrícia Albuquerque
author_facet	Stefânia de Oliveira Frazão Herdson Renney de Sousa Lenise Gonçalves da Silva Jéssica dos Santos Folha Kaio César de Melo Gorgonha Getúlio Pereira de Oliveira Maria Sueli Soares Felipe Ildinete Silva-Pereira Arturo Casadevall André Moraes Nicola Patrícia Albuquerque
author_sort	Stefânia de Oliveira Frazão
title	Laccase Affects the Rate of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Nonlytic Exocytosis from Macrophages
title_short	Laccase Affects the Rate of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Nonlytic Exocytosis from Macrophages
title_full	Laccase Affects the Rate of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Nonlytic Exocytosis from Macrophages
title_fullStr	Laccase Affects the Rate of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Nonlytic Exocytosis from Macrophages
title_full_unstemmed	Laccase Affects the Rate of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Nonlytic Exocytosis from Macrophages
title_sort	laccase affects the rate of <named-content content-type="genus-species">cryptococcus neoformans</named-content> nonlytic exocytosis from macrophages
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/30eb6029a2d44935b1d01fe5154fca5a
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Laccase Affects the Rate of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> Nonlytic Exocytosis from Macrophages

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