The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans

Detalhes bibliográficos
Autor(a) principal: Joffe, Luna S.
Data de Publicação: 2017
Outros Autores: Schneider, Rafael, Lopes, William, Azevedo, Renata, Staats, Charley C., Kmetzsch, Lívia, Schrank, Augusto, Del Poeta, Maurizio, Vainstein, Marilene Henning, Rodrigues, Marcio Lourenço
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/27675
Resumo: Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Biologia Celular de Leveduras Patogênicas Rio de Janeiro, RJ, Brasil.
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spelling Joffe, Luna S.Schneider, RafaelLopes, WilliamAzevedo, RenataStaats, Charley C.Kmetzsch, LíviaSchrank, AugustoDel Poeta, MaurizioVainstein, Marilene HenningRodrigues, Marcio Lourenço2018-07-26T16:28:40Z2018-07-26T16:28:40Z2017JOFFE, L. S. et al. The anti-helminthic compound mebendazole has Multiple antifungal effects against Cryptococcus neoformans. Frontiers in Microbiology, v. 8, p. 1-14, 28 Mar. 2017.1664-302Xhttps://www.arca.fiocruz.br/handle/icict/2767510.3389/fmicb.2017.00535engFrontiers Media SAMebendazolCriptococcoseThe Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformansinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Biologia Celular de Leveduras Patogênicas Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio Grande do Sul. Centro de Biotecnologia. Porto Alegre, RS, Brasil.Universidade Federal do Rio Grande do Sul. Centro de Biotecnologia. Porto Alegre, RS, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio Grande do Sul. Centro de Biotecnologia. Departamento de Biologia Molecular e Biotecnologia. Porto Alegre, RS, Brasil.Universidade Federal do Rio Grande do Sul. Centro de Biotecnologia. Departamento de Biologia Molecular e Biotecnologia. Porto Alegre, RS, Brasil.Universidade Federal do Rio Grande do Sul. Centro de Biotecnologia. Departamento de Biologia Molecular e Biotecnologia. Porto Alegre, RS, Brasil.Veterans Administration Medical Center. Northport, NY, USA / Stony Brook University. Department of Molecular Genetics and Microbiology. Stony Brook, NY, USA.Universidade Federal do Rio Grande do Sul. Centro de Biotecnologia. Departamento de Biologia Molecular e Biotecnologia. Porto Alegre, RS, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Biologia Celular de Leveduras Patogênicas Rio de Janeiro, RJ, Brasil.Cryptococcus neoformans is the most lethal pathogen of the central nervous system. The gold standard treatment of cryptococcosis, a combination of amphotericin B with 5-fluorocytosine, involves broad toxicity, high costs, low efficacy, and limited worldwide availability. Although the need for new antifungals is clear, drug research and development (R&D) is costly and time-consuming. Thus, drug repurposing is an alternative to R&D and to the currently available tools for treating fungal diseases. Here we screened a collection of compounds approved for use in humans seeking for those with anti-cryptococcal activity. We found that benzimidazoles consist of a broad class of chemicals inhibiting C. neoformans growth. Mebendazole and fenbendazole were the most efficient antifungals showing in vitro fungicidal activity. Since previous studies showed that mebendazole reaches the brain in biologically active concentrations, this compound was selected for further studies. Mebendazole showed antifungal activity against phagocytized C. neoformans, affected cryptococcal biofilms profoundly and caused marked morphological alterations in C. neoformans, including reduction of capsular dimensions. Amphotericin B and mebendazole had additive anti-cryptococcal effects. Mebendazole was also active against the C. neoformans sibling species, C. gattii. To further characterize the effects of the drug a random C. gattii mutant library was screened and indicated that the antifungal activity of mebendazole requires previously unknown cryptococcal targets. Our results indicate that mebendazole is as a promising prototype for the future development of anti-cryptococcal drugs.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83101https://www.arca.fiocruz.br/bitstream/icict/27675/1/license.txt425ef259bcb460998407fbfed7c102d0MD51ORIGINALve_Marcio_Rodrigues_etal_CDTS_2017a.pdfve_Marcio_Rodrigues_etal_CDTS_2017a.pdfapplication/pdf3873194https://www.arca.fiocruz.br/bitstream/icict/27675/2/ve_Marcio_Rodrigues_etal_CDTS_2017a.pdf99621cb2d1cf68a20e492eae8b6b1757MD52TEXTve_Marcio_Rodrigues_etal_CDTS_2017a.pdf.txtve_Marcio_Rodrigues_etal_CDTS_2017a.pdf.txtExtracted texttext/plain63926https://www.arca.fiocruz.br/bitstream/icict/27675/3/ve_Marcio_Rodrigues_etal_CDTS_2017a.pdf.txt3ff1485bbbe885b13a2143e918552469MD53icict/276752023-02-14 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dc.title.pt_BR.fl_str_mv The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans
title The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans
spellingShingle The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans
Joffe, Luna S.
Mebendazol
Criptococcose
title_short The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans
title_full The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans
title_fullStr The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans
title_full_unstemmed The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans
title_sort The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans
author Joffe, Luna S.
author_facet Joffe, Luna S.
Schneider, Rafael
Lopes, William
Azevedo, Renata
Staats, Charley C.
Kmetzsch, Lívia
Schrank, Augusto
Del Poeta, Maurizio
Vainstein, Marilene Henning
Rodrigues, Marcio Lourenço
author_role author
author2 Schneider, Rafael
Lopes, William
Azevedo, Renata
Staats, Charley C.
Kmetzsch, Lívia
Schrank, Augusto
Del Poeta, Maurizio
Vainstein, Marilene Henning
Rodrigues, Marcio Lourenço
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Joffe, Luna S.
Schneider, Rafael
Lopes, William
Azevedo, Renata
Staats, Charley C.
Kmetzsch, Lívia
Schrank, Augusto
Del Poeta, Maurizio
Vainstein, Marilene Henning
Rodrigues, Marcio Lourenço
dc.subject.other.pt_BR.fl_str_mv Mebendazol
Criptococcose
topic Mebendazol
Criptococcose
description Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Biologia Celular de Leveduras Patogênicas Rio de Janeiro, RJ, Brasil.
publishDate 2017
dc.date.issued.fl_str_mv 2017
dc.date.accessioned.fl_str_mv 2018-07-26T16:28:40Z
dc.date.available.fl_str_mv 2018-07-26T16:28:40Z
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 JOFFE, L. S. et al. The anti-helminthic compound mebendazole has Multiple antifungal effects against Cryptococcus neoformans. Frontiers in Microbiology, v. 8, p. 1-14, 28 Mar. 2017.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/27675
dc.identifier.issn.pt_BR.fl_str_mv 1664-302X
dc.identifier.doi.none.fl_str_mv 10.3389/fmicb.2017.00535
identifier_str_mv JOFFE, L. S. et al. The anti-helminthic compound mebendazole has Multiple antifungal effects against Cryptococcus neoformans. Frontiers in Microbiology, v. 8, p. 1-14, 28 Mar. 2017.
1664-302X
10.3389/fmicb.2017.00535
url https://www.arca.fiocruz.br/handle/icict/27675
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 Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
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/27675/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/27675/2/ve_Marcio_Rodrigues_etal_CDTS_2017a.pdf
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