Describing the role of Drosophila melanogaster ABC transporters in insecticide biology using CRISPR-Cas9 knockouts

dc.contributor.authorDenecke, Shane
dc.contributor.authorFusetto, Roberto
dc.contributor.authorBatterham, Philip
dc.date.accessioned2024-02-06T21:40:11Z
dc.date.issued2017
dc.date.updated2022-10-09T07:16:30Z
dc.description.abstractABC transporters have a well-established role in drug resistance, effluxing xenobiotics from cells and tissues within the organism. More recently, research has been dedicated to understanding the role insect ABC transporters play in insecticide toxicity, but progress in understanding the contribution of specific transporters has been hampered by the lack of functional genetic tools. Here, we report knockouts of three Drosophila melanogaster ABC transporter genes, Mdr49, Mdr50, and Mdr65, that are homologous to the well-studied mammalian ABCB1 (P-glycoprotein). Each knockout mutant was created in the same wild type background and tested against a panel of insecticides representing different chemical classes. Mdr65 knockouts were more susceptible to all neuroactive insecticides tested, but Mdr49 and Mdr50 knockouts showed increased susceptibility or resistance depending on the insecticide used. Mdr65 was chosen for further analysis. Calculation of LC50 values for the Mdr65 knockout allowed the substrate specificity of this transporter to be examined. No obvious distinguishing structural features were shared among MDR65 substrates. A role for Mdr65 in insecticide transport was confirmed by testing the capacity of the knockout to synergize with the ABC inhibitor verapamil and by measuring the levels of insecticide retained in the body of knockout flies. These data unambiguously establish the influence of ABC transporters on the capacity of wild type D. melanogaster to tolerate insecticide exposure and suggest that both tissue and substrate specificity underpin this capacity.en_AU
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn0965-1748en_AU
dc.identifier.urihttp://hdl.handle.net/1885/313292
dc.language.isoen_AUen_AU
dc.publisherPergamon-Elsevier Ltden_AU
dc.rights© 2017 The authorsen_AU
dc.sourceInsect Biochemistry and Molecular Biologyen_AU
dc.subjectP-glycoproteinen_AU
dc.subjectABCB1en_AU
dc.subjectMulti-drug resistanceen_AU
dc.subjectCRISPR-Cas9en_AU
dc.subjectDrosophila melanogasteren_AU
dc.subjectInsecticide resistanceen_AU
dc.titleDescribing the role of Drosophila melanogaster ABC transporters in insecticide biology using CRISPR-Cas9 knockoutsen_AU
dc.typeJournal articleen_AU
local.bibliographicCitation.lastpage9en_AU
local.bibliographicCitation.startpage1en_AU
local.contributor.affiliationDenecke, Shane, University of Melbourneen_AU
local.contributor.affiliationFusetto, Roberto, University of Melbourneen_AU
local.contributor.affiliationBatterham, Philip, College of Health and Medicine, ANUen_AU
local.contributor.authoremailu4435982@anu.edu.auen_AU
local.contributor.authoruidBatterham, Philip, u4435982en_AU
local.description.embargo2099-12-31
local.description.notesImported from ARIESen_AU
local.identifier.absfor329999 - Other biomedical and clinical sciences not elsewhere classifieden_AU
local.identifier.ariespublicationa383154xPUB12671en_AU
local.identifier.citationvolume91en_AU
local.identifier.doi10.1016/j.ibmb.2017.09.017en_AU
local.identifier.scopusID2-s2.0-85032182078
local.identifier.thomsonIDWOS:000418217700001
local.identifier.uidSubmittedBya383154en_AU
local.publisher.urlhttps://www.sciencedirect.com/en_AU
local.type.statusPublished Versionen_AU

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