Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans

Detalhes bibliográficos
Autor(a) principal: Oliveira, Fabiana Freire M.
Data de Publicação: 2020
Outros Autores: Paes, Hugo Costa, Peconick, Luísa Defranco F., Fonseca, Fernanda L., Marina, Clara Luna Freitas, Bocca, Anamélia Lorenzetti, Homem-de-Mello, Mauricio, Rodrigues, Marcio Lourenço, Albuquerque, Patricia, Nicola, André Moraes, Alspaugh, J. Andrew, Felipe, Maria Sueli S., Fernandes, Larissa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/59626
Resumo: University of Brasília, Brasília. Faculty of Medicine. Campus Darcy Ribeiro. Federal District, DF, Brazil.
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spelling Oliveira, Fabiana Freire M.Paes, Hugo CostaPeconick, Luísa Defranco F.Fonseca, Fernanda L.Marina, Clara Luna FreitasBocca, Anamélia LorenzettiHomem-de-Mello, MauricioRodrigues, Marcio LourençoAlbuquerque, PatriciaNicola, André MoraesAlspaugh, J. AndrewFelipe, Maria Sueli S.Fernandes, Larissa2023-07-18T02:49:23Z2023-07-18T02:49:23Z2020OLIVEIRA, Fabiana Freire M. et al. Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans. Fungal Genetics and Biology, v. 140, p. 1-16, July 2020.1087-1845https://www.arca.fiocruz.br/handle/icict/5962610.1016/J.FGB.2020.1033681096-0937engElsevierAntifungal AgentsAzolesBiosynthetic PathwaysCryptococcosisCryptococcus neoformansEndoplasmic ReticulumErgosterolGene Expression Regulation, FungalHumansMethyltransferasesMutationVirulenceSterol C-24 methyltransferaseErgosterolVirulenceMembrane sterol compositionErg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformansinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversity of Brasília, Brasília. Faculty of Medicine. Campus Darcy Ribeiro. Federal District, DF, Brazil.University of Brasília, Brasília. Faculty of Medicine. Campus Darcy Ribeiro. Federal District, DF, Brazil.University of Brasília. Faculty of Ceilândia. Campus UnB Ceilândia. Federal District, DF, Brazil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.Institute of Biology. Laboratory of Applied Immunology. Federal District, DF, Brazil.Institute of Biology. Laboratory of Applied Immunology. Federal District, DF, Brazil.University of Brasília, Brasília. Faculty of Medicine. Campus Darcy Ribeiro. Federal District, DF, Brazil.Oswaldo Cruz Foundation. Carlos Chagas Institute. Curitiba, PR, Brazil / Federal University of Rio de Janeiro. Microbiology Institute. Rio de Janeiro, RJ, Brazil.University of Brasília. Faculty of Ceilândia. Campus UnB Ceilândia. Federal District, DF, Brazil.University of Brasília, Brasília. Faculty of Medicine. Campus Darcy Ribeiro. Federal District, DF, Brazil.Duke University School of Medicine. Dept. of Medicine Durham. Durham, USA.Catolic University of Brasilia, Campus Asa Norte, Brasília, Federal District, BrazilUniversity of Brasília. Faculty of Ceilândia. Campus UnB Ceilândia. Federal District, DF, Brazil / University of Brasília, Brasília. Faculty of Medicine, Campus Darcy Ribeiro. Federal District, DF, Brazil.Ergosterol is the most important membrane sterol in fungal cells and a component not found in the membranes of human cells. We identified the ERG6 gene in the AIDS-associated fungal pathogen, Cryptococcus neoformans, encoding the sterol C-24 methyltransferase of fungal ergosterol biosynthesis. In this work, we have explored its relationship with high-temperature growth and virulence of C. neoformans by the construction of a loss-of-function mutant. In contrast to other genes involved in ergosterol biosynthesis, C. neoformans ERG6 is not essential for growth under permissive conditions in vitro. However, the erg6 mutant displayed impaired thermotolerance and increased susceptibility to osmotic and oxidative stress, as well as to different antifungal drugs. Total lipid analysis demonstrated a decrease in the erg6Δ strain membrane ergosterol content. In addition, this mutant strain was avirulent in an invertebrate model of C. neoformans infection. C. neoformans Erg6 was cyto-localized in the endoplasmic reticulum and Golgi complex. Our results demonstrate that Erg6 is crucial for growth at high temperature and virulence, likely due to its effects on C. neoformans membrane integrity and dynamics. These pathogen-focused investigations into ergosterol biosynthetic pathway components reinforce the multiple roles of ergosterol in the response of diverse fungal species to alterations in the environment, especially that of the infected host. These studies open perspectives to understand the participation of ergosterol in mechanism of resistance to azole and polyene drugs. Observed synergistic growth defects with co-inhibition of Erg6 and other components of the ergosterol biosynthesis pathway suggests novel approaches to treatment in human fungal infections.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/59626/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINAL10.1016_j.fgb.2020.103368.pdfapplication/pdf2575391https://www.arca.fiocruz.br/bitstream/icict/59626/2/10.1016_j.fgb.2020.103368.pdf19882ab4ee086188ec1ac633af6d0bc2MD52icict/596262023-07-18 22:22:21.039oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-07-19T01:22:21Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans
title Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans
spellingShingle Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans
Oliveira, Fabiana Freire M.
Antifungal Agents
Azoles
Biosynthetic Pathways
Cryptococcosis
Cryptococcus neoformans
Endoplasmic Reticulum
Ergosterol
Gene Expression Regulation, Fungal
Humans
Methyltransferases
Mutation
Virulence
Sterol C-24 methyltransferase
Ergosterol
Virulence
Membrane sterol composition
title_short Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans
title_full Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans
title_fullStr Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans
title_full_unstemmed Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans
title_sort Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans
author Oliveira, Fabiana Freire M.
author_facet Oliveira, Fabiana Freire M.
Paes, Hugo Costa
Peconick, Luísa Defranco F.
Fonseca, Fernanda L.
Marina, Clara Luna Freitas
Bocca, Anamélia Lorenzetti
Homem-de-Mello, Mauricio
Rodrigues, Marcio Lourenço
Albuquerque, Patricia
Nicola, André Moraes
Alspaugh, J. Andrew
Felipe, Maria Sueli S.
Fernandes, Larissa
author_role author
author2 Paes, Hugo Costa
Peconick, Luísa Defranco F.
Fonseca, Fernanda L.
Marina, Clara Luna Freitas
Bocca, Anamélia Lorenzetti
Homem-de-Mello, Mauricio
Rodrigues, Marcio Lourenço
Albuquerque, Patricia
Nicola, André Moraes
Alspaugh, J. Andrew
Felipe, Maria Sueli S.
Fernandes, Larissa
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Oliveira, Fabiana Freire M.
Paes, Hugo Costa
Peconick, Luísa Defranco F.
Fonseca, Fernanda L.
Marina, Clara Luna Freitas
Bocca, Anamélia Lorenzetti
Homem-de-Mello, Mauricio
Rodrigues, Marcio Lourenço
Albuquerque, Patricia
Nicola, André Moraes
Alspaugh, J. Andrew
Felipe, Maria Sueli S.
Fernandes, Larissa
dc.subject.mesh.en_US.fl_str_mv Antifungal Agents
Azoles
Biosynthetic Pathways
Cryptococcosis
Cryptococcus neoformans
Endoplasmic Reticulum
Ergosterol
Gene Expression Regulation, Fungal
Humans
Methyltransferases
Mutation
Virulence
topic Antifungal Agents
Azoles
Biosynthetic Pathways
Cryptococcosis
Cryptococcus neoformans
Endoplasmic Reticulum
Ergosterol
Gene Expression Regulation, Fungal
Humans
Methyltransferases
Mutation
Virulence
Sterol C-24 methyltransferase
Ergosterol
Virulence
Membrane sterol composition
dc.subject.en.en_US.fl_str_mv Sterol C-24 methyltransferase
Ergosterol
Virulence
Membrane sterol composition
description University of Brasília, Brasília. Faculty of Medicine. Campus Darcy Ribeiro. Federal District, DF, Brazil.
publishDate 2020
dc.date.issued.fl_str_mv 2020
dc.date.accessioned.fl_str_mv 2023-07-18T02:49:23Z
dc.date.available.fl_str_mv 2023-07-18T02:49:23Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv OLIVEIRA, Fabiana Freire M. et al. Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans. Fungal Genetics and Biology, v. 140, p. 1-16, July 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/59626
dc.identifier.issn.en_US.fl_str_mv 1087-1845
dc.identifier.doi.none.fl_str_mv 10.1016/J.FGB.2020.103368
dc.identifier.eissn.none.fl_str_mv 1096-0937
identifier_str_mv OLIVEIRA, Fabiana Freire M. et al. Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans. Fungal Genetics and Biology, v. 140, p. 1-16, July 2020.
1087-1845
10.1016/J.FGB.2020.103368
1096-0937
url https://www.arca.fiocruz.br/handle/icict/59626
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
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reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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