Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

Detalhes bibliográficos
Autor(a) principal: Mor, Visesato
Data de Publicação: 2015
Outros Autores: Rella, Antonella, Farnoud, Amir M., Singh, Ashutosh, Munshi, Mansa, Bryan, Arielle, Naseem, Shamoon, Konopka, James B., Ojima, Iwao, Bullesbach, Erika, Ashbaugh, Alan, Linke, Michael J., Cushion, Melanie, Collins, Margaret, Ananthula, Hari Krishna, Sallans, Larry, Desai, Pankaj B., Wiederhold, Nathan P., Fothergill, Annette W., Kirkpatrick, William R., Patterson, Thomas, Wong, Lai Hong, Sinha, Sunita, Giaever, Guri, Nislow, Corey, Flaherty, Patrick, Pan, Xuewen, Cesar, Gabriele Vargas, de Melo Tavares, Patricia, Frases, Susana, Miranda, Kildare, Rodrigues, Marcio Lourenço, Luberto, Chiara, Nimrichter, Leonardo, Del Poeta, Maurizio
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/27680
Resumo: Visesato Mor, a; Antonella Rella, a; Amir M. Farnoud, a; Ashutosh Singh, a; Mansa Munshi, a; Arielle Bryan, a; Shamoon Naseem, a; James B. Konopka, a; Iwao Ojima, b; Erika Bullesbach, c; Alan Ashbaugh, d; Michael J. Linke, d,e; Melanie Cushion, d,e; Margaret Collins, e; Hari Krishna Ananthula, f; Larry Sallans, q; Pankaj B. Desai, f; Nathan P. Wiederhold, g; Annette W. Fothergill, g; William R. Kirkpatrick, h; Thomas Patterson, h; Lai Hong Wong, i; Sunita Sinha, i; Guri Giaever, i; Corey Nislow, i; Patrick Flaherty, j; Xuewen Pan, k; Gabriele Vargas Cesar, l; Patricia de Melo Tavares, l; Susana Frases, m; Kildare Miranda, l,n; Marcio L. Rodrigues, l,o; Chiara Luberto, p; Leonardo Nimrichter, l; Maurizio Del Poeta, a. Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA a; Department of Chemistry and Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, New York, USA b; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA c; Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA d; University of Cincinnati College of Medicine, Cincinnati, Ohio, USA e; Department of Pharmaceutical Sciences, University of Cincinnati, Cincinnati, Ohio, USA f; Department of Pathology, Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA g; Division of Infectious Diseases, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA h; Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Colombia, Canada i; Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts, USA j; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA k; Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil i; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil m ; Diretoria de Metrologia Aplicada a Ciências da Vida, Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMETRO), Xerém, Rio de Janeiro, Brazil n; Fundação Oswaldo Cruz (Fiocruz), Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Rio de Janeiro, Brazil o; Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, USA p; Department of Chemistry, University of Cincinnati, Cincinnati, Ohio, USA q.
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spelling Mor, VisesatoRella, AntonellaFarnoud, Amir M.Singh, AshutoshMunshi, MansaBryan, ArielleNaseem, ShamoonKonopka, James B.Ojima, IwaoBullesbach, ErikaAshbaugh, AlanLinke, Michael J.Cushion, MelanieCollins, MargaretAnanthula, Hari KrishnaSallans, LarryDesai, Pankaj B.Wiederhold, Nathan P.Fothergill, Annette W.Kirkpatrick, William R.Patterson, ThomasWong, Lai HongSinha, SunitaGiaever, GuriNislow, CoreyFlaherty, PatrickPan, XuewenCesar, Gabriele Vargasde Melo Tavares, PatriciaFrases, SusanaMiranda, KildareRodrigues, Marcio LourençoLuberto, ChiaraNimrichter, LeonardoDel Poeta, Maurizio2018-07-26T17:44:12Z2018-07-26T17:44:12Z2015MOR, V. et al. Identification of a new class of antifungals targeting the synthesis of fungal sphingolipids. mBio, v. 6, n. 3, p. 1-17, 2015.2150-7511https://www.arca.fiocruz.br/handle/icict/2768010.1128/mBio.00647-15Visesato Mor, a; Antonella Rella, a; Amir M. Farnoud, a; Ashutosh Singh, a; Mansa Munshi, a; Arielle Bryan, a; Shamoon Naseem, a; James B. Konopka, a; Iwao Ojima, b; Erika Bullesbach, c; Alan Ashbaugh, d; Michael J. Linke, d,e; Melanie Cushion, d,e; Margaret Collins, e; Hari Krishna Ananthula, f; Larry Sallans, q; Pankaj B. Desai, f; Nathan P. Wiederhold, g; Annette W. Fothergill, g; William R. Kirkpatrick, h; Thomas Patterson, h; Lai Hong Wong, i; Sunita Sinha, i; Guri Giaever, i; Corey Nislow, i; Patrick Flaherty, j; Xuewen Pan, k; Gabriele Vargas Cesar, l; Patricia de Melo Tavares, l; Susana Frases, m; Kildare Miranda, l,n; Marcio L. Rodrigues, l,o; Chiara Luberto, p; Leonardo Nimrichter, l; Maurizio Del Poeta, a. Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA a; Department of Chemistry and Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, New York, USA b; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA c; Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA d; University of Cincinnati College of Medicine, Cincinnati, Ohio, USA e; Department of Pharmaceutical Sciences, University of Cincinnati, Cincinnati, Ohio, USA f; Department of Pathology, Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA g; Division of Infectious Diseases, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA h; Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Colombia, Canada i; Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts, USA j; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA k; Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil i; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil m ; Diretoria de Metrologia Aplicada a Ciências da Vida, Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMETRO), Xerém, Rio de Janeiro, Brazil n; Fundação Oswaldo Cruz (Fiocruz), Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Rio de Janeiro, Brazil o; Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, USA p; Department of Chemistry, University of Cincinnati, Cincinnati, Ohio, USA q.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. Rio de Janeiro, RJ, Brasil.Múltipla - ver notasRecent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N'-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N'-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM.engAmerican Society for MicrobiologyIdentification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipidsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleAntifungals TargetingSynthesis of Fungal Sphingolipidsinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids
title Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids
spellingShingle Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids
Mor, Visesato
Antifungals Targeting
Synthesis of Fungal Sphingolipids
title_short Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids
title_full Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids
title_fullStr Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids
title_full_unstemmed Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids
title_sort Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids
author Mor, Visesato
author_facet Mor, Visesato
Rella, Antonella
Farnoud, Amir M.
Singh, Ashutosh
Munshi, Mansa
Bryan, Arielle
Naseem, Shamoon
Konopka, James B.
Ojima, Iwao
Bullesbach, Erika
Ashbaugh, Alan
Linke, Michael J.
Cushion, Melanie
Collins, Margaret
Ananthula, Hari Krishna
Sallans, Larry
Desai, Pankaj B.
Wiederhold, Nathan P.
Fothergill, Annette W.
Kirkpatrick, William R.
Patterson, Thomas
Wong, Lai Hong
Sinha, Sunita
Giaever, Guri
Nislow, Corey
Flaherty, Patrick
Pan, Xuewen
Cesar, Gabriele Vargas
de Melo Tavares, Patricia
Frases, Susana
Miranda, Kildare
Rodrigues, Marcio Lourenço
Luberto, Chiara
Nimrichter, Leonardo
Del Poeta, Maurizio
author_role author
author2 Rella, Antonella
Farnoud, Amir M.
Singh, Ashutosh
Munshi, Mansa
Bryan, Arielle
Naseem, Shamoon
Konopka, James B.
Ojima, Iwao
Bullesbach, Erika
Ashbaugh, Alan
Linke, Michael J.
Cushion, Melanie
Collins, Margaret
Ananthula, Hari Krishna
Sallans, Larry
Desai, Pankaj B.
Wiederhold, Nathan P.
Fothergill, Annette W.
Kirkpatrick, William R.
Patterson, Thomas
Wong, Lai Hong
Sinha, Sunita
Giaever, Guri
Nislow, Corey
Flaherty, Patrick
Pan, Xuewen
Cesar, Gabriele Vargas
de Melo Tavares, Patricia
Frases, Susana
Miranda, Kildare
Rodrigues, Marcio Lourenço
Luberto, Chiara
Nimrichter, Leonardo
Del Poeta, Maurizio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Mor, Visesato
Rella, Antonella
Farnoud, Amir M.
Singh, Ashutosh
Munshi, Mansa
Bryan, Arielle
Naseem, Shamoon
Konopka, James B.
Ojima, Iwao
Bullesbach, Erika
Ashbaugh, Alan
Linke, Michael J.
Cushion, Melanie
Collins, Margaret
Ananthula, Hari Krishna
Sallans, Larry
Desai, Pankaj B.
Wiederhold, Nathan P.
Fothergill, Annette W.
Kirkpatrick, William R.
Patterson, Thomas
Wong, Lai Hong
Sinha, Sunita
Giaever, Guri
Nislow, Corey
Flaherty, Patrick
Pan, Xuewen
Cesar, Gabriele Vargas
de Melo Tavares, Patricia
Frases, Susana
Miranda, Kildare
Rodrigues, Marcio Lourenço
Luberto, Chiara
Nimrichter, Leonardo
Del Poeta, Maurizio
dc.subject.en.pt_BR.fl_str_mv Antifungals Targeting
Synthesis of Fungal Sphingolipids
topic Antifungals Targeting
Synthesis of Fungal Sphingolipids
description Visesato Mor, a; Antonella Rella, a; Amir M. Farnoud, a; Ashutosh Singh, a; Mansa Munshi, a; Arielle Bryan, a; Shamoon Naseem, a; James B. Konopka, a; Iwao Ojima, b; Erika Bullesbach, c; Alan Ashbaugh, d; Michael J. Linke, d,e; Melanie Cushion, d,e; Margaret Collins, e; Hari Krishna Ananthula, f; Larry Sallans, q; Pankaj B. Desai, f; Nathan P. Wiederhold, g; Annette W. Fothergill, g; William R. Kirkpatrick, h; Thomas Patterson, h; Lai Hong Wong, i; Sunita Sinha, i; Guri Giaever, i; Corey Nislow, i; Patrick Flaherty, j; Xuewen Pan, k; Gabriele Vargas Cesar, l; Patricia de Melo Tavares, l; Susana Frases, m; Kildare Miranda, l,n; Marcio L. Rodrigues, l,o; Chiara Luberto, p; Leonardo Nimrichter, l; Maurizio Del Poeta, a. Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA a; Department of Chemistry and Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, New York, USA b; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA c; Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA d; University of Cincinnati College of Medicine, Cincinnati, Ohio, USA e; Department of Pharmaceutical Sciences, University of Cincinnati, Cincinnati, Ohio, USA f; Department of Pathology, Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA g; Division of Infectious Diseases, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA h; Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Colombia, Canada i; Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts, USA j; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA k; Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil i; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil m ; Diretoria de Metrologia Aplicada a Ciências da Vida, Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMETRO), Xerém, Rio de Janeiro, Brazil n; Fundação Oswaldo Cruz (Fiocruz), Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Rio de Janeiro, Brazil o; Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, USA p; Department of Chemistry, University of Cincinnati, Cincinnati, Ohio, USA q.
publishDate 2015
dc.date.issued.fl_str_mv 2015
dc.date.accessioned.fl_str_mv 2018-07-26T17:44:12Z
dc.date.available.fl_str_mv 2018-07-26T17:44:12Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv MOR, V. et al. Identification of a new class of antifungals targeting the synthesis of fungal sphingolipids. mBio, v. 6, n. 3, p. 1-17, 2015.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/27680
dc.identifier.issn.pt_BR.fl_str_mv 2150-7511
dc.identifier.doi.none.fl_str_mv 10.1128/mBio.00647-15
identifier_str_mv MOR, V. et al. Identification of a new class of antifungals targeting the synthesis of fungal sphingolipids. mBio, v. 6, n. 3, p. 1-17, 2015.
2150-7511
10.1128/mBio.00647-15
url https://www.arca.fiocruz.br/handle/icict/27680
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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)
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bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/27680/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/27680/2/ve_Marcio_Rodrigues_etal_CDTS_2015b.pdf
https://www.arca.fiocruz.br/bitstream/icict/27680/3/ve_Marcio_Rodrigues_etal_CDTS_2015b.pdf.txt
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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