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

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dc.contributor.authorAlmeida, Ludimila Dias
dc.contributor.authorSilva, Ali Salim Faraj
dc.contributor.authorMota, Daniel Calixto
dc.contributor.authorVasconcelos, Adrielle Ayumi
dc.contributor.authorCamargo, Antônio Pedro
dc.contributor.authorPires, Gabriel Silva
dc.contributor.authorFurlan, Monique
dc.contributor.authorDa Cunha Freire, Helena Martins Ribeiro
dc.contributor.authorKlippel, Angélica Hollunder [UNESP]
dc.contributor.authorSilva, Suélen Fernandes [UNESP]
dc.contributor.authorZanelli, Cleslei Fernando [UNESP]
dc.contributor.authorCarazzolle, Marcelo Falsarella
dc.contributor.authorOliver, Stephen G.
dc.contributor.authorBilsland, Elizabeth
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversity of Cambridge
dc.date.accessioned2022-04-29T08:46:14Z
dc.date.available2022-04-29T08:46:14Z
dc.date.issued2021-12-01
dc.description.abstractThe 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.en
dc.description.affiliationSynthetic Biology Laboratory Department of Structural and Functional Biology Institute of Biology University of Campinas-UNICAMP, São Paulo
dc.description.affiliationLaboratory of Genomics and BioEnergy Department of Genetics Evolution Microbiology and Immunology Institute of Biology University of Campinas-UNICAMP, São Paulo
dc.description.affiliationSchool of Pharmaceutical Sciences São Paulo State University-UNESP, São Paulo
dc.description.affiliationChemistry Institute São Paulo State University-UNESP, São Paulo
dc.description.affiliationCambridge Systems Biology Centre University of Cambridge
dc.description.affiliationDepartment of Biochemistry University of Cambridge
dc.description.affiliationUnespSchool of Pharmaceutical Sciences São Paulo State University-UNESP, São Paulo
dc.description.affiliationUnespChemistry Institute São Paulo State University-UNESP, São Paulo
dc.identifierhttp://dx.doi.org/10.1128/mbio.03221-21
dc.identifier.citationmBio, v. 12, n. 6, 2021.
dc.identifier.doi10.1128/mbio.03221-21
dc.identifier.issn2150-7511
dc.identifier.issn2161-2129
dc.identifier.scopus2-s2.0-85121978014
dc.identifier.urihttp://hdl.handle.net/11449/231580
dc.language.isoeng
dc.relation.ispartofmBio
dc.sourceScopus
dc.subjectDrug efflux
dc.subjectDrug transport
dc.subjectDrug uptake
dc.subjectGenetic interactions
dc.subjectNonessential transporter double-deletion library
dc.subjectPlasma membrane transporter
dc.subjectSaccharomyces cerevisiae
dc.subjectXenobiotics
dc.subjectYeast
dc.titleYeast Double Transporter Gene Deletion Library for Identification of Xenobiotic Carriers in Low or High Throughputen
dc.typeArtigo

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