Yeast Double Transporter Gene Deletion Library for Identification of Xenobiotic Carriers in Low or High Throughput

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Autor(es): dc.contributorUniversidade Estadual de Campinas (UNICAMP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversity of Cambridge-
Autor(es): dc.creatorAlmeida, Ludimila Dias-
Autor(es): dc.creatorSilva, Ali Salim Faraj-
Autor(es): dc.creatorMota, Daniel Calixto-
Autor(es): dc.creatorVasconcelos, Adrielle Ayumi-
Autor(es): dc.creatorCamargo, Antônio Pedro-
Autor(es): dc.creatorPires, Gabriel Silva-
Autor(es): dc.creatorFurlan, Monique-
Autor(es): dc.creatorDa Cunha Freire, Helena Martins Ribeiro-
Autor(es): dc.creatorKlippel, Angélica Hollunder-
Autor(es): dc.creatorSilva, Suélen Fernandes-
Autor(es): dc.creatorZanelli, Cleslei Fernando-
Autor(es): dc.creatorCarazzolle, Marcelo Falsarella-
Autor(es): dc.creatorOliver, Stephen G.-
Autor(es): dc.creatorBilsland, Elizabeth-
Data de aceite: dc.date.accessioned2025-08-21T22:37:54Z-
Data de disponibilização: dc.date.available2025-08-21T22:37:54Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2021-11-30-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1128/mbio.03221-21-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/231580-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/231580-
Descrição: dc.descriptionThe routes of uptake and efflux should be considered when developing new drugs so that they can effectively address their intracellular targets. As a general rule, drugs appear to enter cells via protein carriers that normally carry nutrients or metabolites. A previously developed pipeline that searched for drug transporters using Saccharomyces cerevisiae mutants carrying single-gene deletions identified import routes for most compounds tested. However, due to the redundancy of transporter functions, we propose that this methodology can be improved by utilizing double mutant strains in both low- and high-throughput screens. We constructed a library of over 14,000 strains harboring double deletions of genes encoding 122 nonessential plasma membrane transporters and performed low- and high-throughput screens identifying possible drug import routes for 23 compounds. In addition, the high-throughput assay enabled the identification of putative efflux routes for 21 compounds. Focusing on azole antifungals, we were able to identify the involvement of the myo-inositol transporter, Itr1p, in the uptake of these molecules and to confirm the role of Pdr5p in their export.-
Descrição: dc.descriptionSynthetic Biology Laboratory Department of Structural and Functional Biology Institute of Biology University of Campinas-UNICAMP, São Paulo-
Descrição: dc.descriptionLaboratory of Genomics and BioEnergy Department of Genetics Evolution Microbiology and Immunology Institute of Biology University of Campinas-UNICAMP, São Paulo-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences São Paulo State University-UNESP, São Paulo-
Descrição: dc.descriptionChemistry Institute São Paulo State University-UNESP, São Paulo-
Descrição: dc.descriptionCambridge Systems Biology Centre University of Cambridge-
Descrição: dc.descriptionDepartment of Biochemistry University of Cambridge-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences São Paulo State University-UNESP, São Paulo-
Descrição: dc.descriptionChemistry Institute São Paulo State University-UNESP, São Paulo-
Idioma: dc.languageen-
Relação: dc.relationmBio-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectDrug efflux-
Palavras-chave: dc.subjectDrug transport-
Palavras-chave: dc.subjectDrug uptake-
Palavras-chave: dc.subjectGenetic interactions-
Palavras-chave: dc.subjectNonessential transporter double-deletion library-
Palavras-chave: dc.subjectPlasma membrane transporter-
Palavras-chave: dc.subjectSaccharomyces cerevisiae-
Palavras-chave: dc.subjectXenobiotics-
Palavras-chave: dc.subjectYeast-
Título: dc.titleYeast Double Transporter Gene Deletion Library for Identification of Xenobiotic Carriers in Low or High Throughput-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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