Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans

Detalhes bibliográficos
Autor(a) principal: Raj, Shriya
Data de Publicação: 2017
Outros Autores: Nazemidashtarjandi, Saeed, Kim, Jihyun, Joffe, Luna, Zhang, Xiaoxue, Singh, Ashutosh, Mor, Visesato, Desmarini, Desmarini, Djordjevic, Julianne, Raleigh, Daniel P., Rodrigues, Marcio L., London, Erwin, Del Poeta, Maurizio, Farnoud, Amir M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/59650
Resumo: Department of Mycology. Institut Pasteur. Paris, France.
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spelling Raj, ShriyaNazemidashtarjandi, SaeedKim, JihyunJoffe, LunaZhang, XiaoxueSingh, AshutoshMor, VisesatoDesmarini, DesmariniDjordjevic, JulianneRaleigh, Daniel P.Rodrigues, Marcio L.London, ErwinDel Poeta, MaurizioFarnoud, Amir M.2023-07-18T08:34:51Z2023-07-18T08:34:51Z2017RAJ, Shriya et al. Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans. Biochimica et Biophysica Acta - Biomembranes, v. 1859, n. 11, p. 2224-2233, Nov. 2017.0005-2736https://www.arca.fiocruz.br/handle/icict/5965010.1016/J.BBAMEM.2017.08.0171879-2642engElsevierAnimalsBiophysical PhenomenaCell MembraneCryptococcosisCryptococcus neoformansFemaleGlucosylceramidesMiceMice, Inbred CBAOrganisms Genetically ModifiedVirulenceSphingolipidFungiInfectious diseasePlasma membraneCryptococcusGlucosylceramideChanges in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformansinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleDepartment of Mycology. Institut Pasteur. Paris, France.Department of Chemical and Biomolecular Engineering. Ohio University. Athens, USA.Department of Chemistry and Biochemistry. Stony Brook University. Stony Brook, USA.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral, Rio de Janeiro, RJ, Brazil.Department of Chemistry and Biochemistry. Stony Brook University. Stony Brook, USA.Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, USA.Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, USA.Fungal Pathogenesis Laboratory. Centre for Infectious Diseases and Microbiology. The Westmead Institute for Medical Research. Westmead, Australia.Fungal Pathogenesis Laboratory. Centre for Infectious Diseases and Microbiology. The Westmead Institute for Medical Research. Westmead, Australia / Westmead Clinical School. University of Sydney at Westmead Hospital. Westmead, Australia / Marie Bashir Institute for Infectious Diseases and Biosecurity. University of Sydney, Australia.Department of Chemistry and Biochemistry. Stony Brook University. Stony Brook, USA.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Rio de Janeiro, RJ, Brazil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brazil.Department of Chemistry and Biochemistry. Stony Brook University. Stony Brook, USA.Department of Molecular Genetics and Microbiology. Stony Brook University. Stony Brook, USA / Veterans Administration Medical Center. Northport, USA / Division of Infectious Diseases. Stony Brook University. Stony Brook, USA.Department of Chemical and Biomolecular Engineering. Ohio University. Athens, USA.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.Fungal glucosylceramide (GlcCer) is a plasma membrane sphingolipid in which the sphingosine backbone is unsaturated in carbon position 8 (C8) and methylated in carbon position 9 (C9). Studies in the fungal pathogen, Cryptococcus neoformans, have shown that loss of GlcCer synthase activity results in complete loss of virulence in the mouse model. However, whether the loss of virulence is due to the lack of the enzyme or to the loss of the sphingolipid is not known. In this study, we used genetic engineering to alter the chemical structure of fungal GlcCer and studied its effect on fungal growth and pathogenicity. Here we show that unsaturation in C8 and methylation in C9 is required for virulence in the mouse model without affecting fungal growth in vitro or common virulence factors. However, changes in GlcCer structure led to a dramatic susceptibility to membrane stressors resulting in increased cell membrane permeability and rendering the fungal mutant unable to grow within host macrophages. Biophysical studies using synthetic vesicles containing GlcCer revealed that the saturated and unmethylated sphingolipid formed vesicles with higher lipid order that were more likely to phase separate into ordered domains. Taken together, these studies show for the first time that a specific structure of GlcCer is a major regulator of membrane permeability required for fungal pathogenicity.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/59650/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINAL10.1016_j.bbamem.2017.08.017.pdfapplication/pdf929360https://www.arca.fiocruz.br/bitstream/icict/59650/2/10.1016_j.bbamem.2017.08.017.pdf16dc6410757c1c4c83c3ab6fa0b5fe9cMD52icict/596502023-07-18 15:39:02.76oai:www.arca.fiocruz.br:icict/59650Tk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-07-18T18:39:02Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans
title Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans
spellingShingle Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans
Raj, Shriya
Animals
Biophysical Phenomena
Cell Membrane
Cryptococcosis
Cryptococcus neoformans
Female
Glucosylceramides
Mice
Mice, Inbred CBA
Organisms Genetically Modified
Virulence
Sphingolipid
Fungi
Infectious disease
Plasma membrane
Cryptococcus
Glucosylceramide
title_short Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans
title_full Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans
title_fullStr Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans
title_full_unstemmed Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans
title_sort Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans
author Raj, Shriya
author_facet Raj, Shriya
Nazemidashtarjandi, Saeed
Kim, Jihyun
Joffe, Luna
Zhang, Xiaoxue
Singh, Ashutosh
Mor, Visesato
Desmarini, Desmarini
Djordjevic, Julianne
Raleigh, Daniel P.
Rodrigues, Marcio L.
London, Erwin
Del Poeta, Maurizio
Farnoud, Amir M.
author_role author
author2 Nazemidashtarjandi, Saeed
Kim, Jihyun
Joffe, Luna
Zhang, Xiaoxue
Singh, Ashutosh
Mor, Visesato
Desmarini, Desmarini
Djordjevic, Julianne
Raleigh, Daniel P.
Rodrigues, Marcio L.
London, Erwin
Del Poeta, Maurizio
Farnoud, Amir M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Raj, Shriya
Nazemidashtarjandi, Saeed
Kim, Jihyun
Joffe, Luna
Zhang, Xiaoxue
Singh, Ashutosh
Mor, Visesato
Desmarini, Desmarini
Djordjevic, Julianne
Raleigh, Daniel P.
Rodrigues, Marcio L.
London, Erwin
Del Poeta, Maurizio
Farnoud, Amir M.
dc.subject.mesh.en_US.fl_str_mv Animals
Biophysical Phenomena
Cell Membrane
Cryptococcosis
Cryptococcus neoformans
Female
Glucosylceramides
Mice
Mice, Inbred CBA
Organisms Genetically Modified
Virulence
topic Animals
Biophysical Phenomena
Cell Membrane
Cryptococcosis
Cryptococcus neoformans
Female
Glucosylceramides
Mice
Mice, Inbred CBA
Organisms Genetically Modified
Virulence
Sphingolipid
Fungi
Infectious disease
Plasma membrane
Cryptococcus
Glucosylceramide
dc.subject.en.en_US.fl_str_mv Sphingolipid
Fungi
Infectious disease
Plasma membrane
Cryptococcus
Glucosylceramide
description Department of Mycology. Institut Pasteur. Paris, France.
publishDate 2017
dc.date.issued.fl_str_mv 2017
dc.date.accessioned.fl_str_mv 2023-07-18T08:34:51Z
dc.date.available.fl_str_mv 2023-07-18T08:34:51Z
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 RAJ, Shriya et al. Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans. Biochimica et Biophysica Acta - Biomembranes, v. 1859, n. 11, p. 2224-2233, Nov. 2017.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/59650
dc.identifier.issn.en_US.fl_str_mv 0005-2736
dc.identifier.doi.none.fl_str_mv 10.1016/J.BBAMEM.2017.08.017
dc.identifier.eissn.none.fl_str_mv 1879-2642
identifier_str_mv RAJ, Shriya et al. Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans. Biochimica et Biophysica Acta - Biomembranes, v. 1859, n. 11, p. 2224-2233, Nov. 2017.
0005-2736
10.1016/J.BBAMEM.2017.08.017
1879-2642
url https://www.arca.fiocruz.br/handle/icict/59650
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)
instacron:FIOCRUZ
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reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/59650/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/59650/2/10.1016_j.bbamem.2017.08.017.pdf
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repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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