Author | Mor, Visesato | |
Author | Rella, Antonella | |
Author | Farnoud, Amir M. | |
Author | Singh, Ashutosh | |
Author | Munshi, Mansa | |
Author | Bryan, Arielle | |
Author | Naseem, Shamoon | |
Author | Konopka, James B. | |
Author | Ojima, Iwao | |
Author | Bullesbach, Erika | |
Author | Ashbaugh, Alan | |
Author | Linke, Michael J. | |
Author | Cushion, Melanie | |
Author | Collins, Margaret | |
Author | Ananthula, Hari Krishna | |
Author | Sallans, Larry | |
Author | Desai, Pankaj B. | |
Author | Wiederhold, Nathan P. | |
Author | Fothergill, Annette W. | |
Author | Kirkpatrick, William R. | |
Author | Patterson, Thomas | |
Author | Wong, Lai Hong | |
Author | Sinha, Sunita | |
Author | Giaever, Guri | |
Author | Nislow, Corey | |
Author | Flaherty, Patrick | |
Author | Pan, Xuewen | |
Author | Cesar, Gabriele Vargas | |
Author | de Melo Tavares, Patricia | |
Author | Frases, Susana | |
Author | Miranda, Kildare | |
Author | Rodrigues, Marcio Lourenço | |
Author | Luberto, Chiara | |
Author | Nimrichter, Leonardo | |
Author | Del Poeta, Maurizio | |
Access date | 2018-07-26T17:44:12Z | |
Available date | 2018-07-26T17:44:12Z | |
Document date | 2015 | |
Citation | 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. | pt_BR |
ISSN | 2150-7511 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/27680 | |
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. | pt_BR |
Language | eng | pt_BR |
Publisher | American Society for Microbiology | pt_BR |
Rights | open access | pt_BR |
Title | Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids | pt_BR |
Type | Article | pt_BR |
DOI | 10.1128/mBio.00647-15 | |
Abstract | Recent 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. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | Múltipla - ver notas | pt_BR |
Subject | Antifungals Targeting | pt_BR |
Subject | Synthesis of Fungal Sphingolipids | pt_BR |