Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , , , |
| 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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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. |
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2020 |
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2020 |
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2023-07-18T02:49:23Z |
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2023-07-18T02:49:23Z |
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info:eu-repo/semantics/article |
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article |
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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. |
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https://www.arca.fiocruz.br/handle/icict/59626 |
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1087-1845 |
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10.1016/J.FGB.2020.103368 |
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1096-0937 |
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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 |
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