Describing the role of Drosophila melanogaster ABC transporters in insecticide biology using CRISPR-Cas9 knockouts
dc.contributor.author | Denecke, Shane | |
dc.contributor.author | Fusetto, Roberto | |
dc.contributor.author | Batterham, Philip | |
dc.date.accessioned | 2024-02-06T21:40:11Z | |
dc.date.issued | 2017 | |
dc.date.updated | 2022-10-09T07:16:30Z | |
dc.description.abstract | ABC 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.mimetype | application/pdf | en_AU |
dc.identifier.issn | 0965-1748 | en_AU |
dc.identifier.uri | http://hdl.handle.net/1885/313292 | |
dc.language.iso | en_AU | en_AU |
dc.publisher | Pergamon-Elsevier Ltd | en_AU |
dc.rights | © 2017 The authors | en_AU |
dc.source | Insect Biochemistry and Molecular Biology | en_AU |
dc.subject | P-glycoprotein | en_AU |
dc.subject | ABCB1 | en_AU |
dc.subject | Multi-drug resistance | en_AU |
dc.subject | CRISPR-Cas9 | en_AU |
dc.subject | Drosophila melanogaster | en_AU |
dc.subject | Insecticide resistance | en_AU |
dc.title | Describing the role of Drosophila melanogaster ABC transporters in insecticide biology using CRISPR-Cas9 knockouts | en_AU |
dc.type | Journal article | en_AU |
local.bibliographicCitation.lastpage | 9 | en_AU |
local.bibliographicCitation.startpage | 1 | en_AU |
local.contributor.affiliation | Denecke, Shane, University of Melbourne | en_AU |
local.contributor.affiliation | Fusetto, Roberto, University of Melbourne | en_AU |
local.contributor.affiliation | Batterham, Philip, College of Health and Medicine, ANU | en_AU |
local.contributor.authoremail | u4435982@anu.edu.au | en_AU |
local.contributor.authoruid | Batterham, Philip, u4435982 | en_AU |
local.description.embargo | 2099-12-31 | |
local.description.notes | Imported from ARIES | en_AU |
local.identifier.absfor | 329999 - Other biomedical and clinical sciences not elsewhere classified | en_AU |
local.identifier.ariespublication | a383154xPUB12671 | en_AU |
local.identifier.citationvolume | 91 | en_AU |
local.identifier.doi | 10.1016/j.ibmb.2017.09.017 | en_AU |
local.identifier.scopusID | 2-s2.0-85032182078 | |
local.identifier.thomsonID | WOS:000418217700001 | |
local.identifier.uidSubmittedBy | a383154 | en_AU |
local.publisher.url | https://www.sciencedirect.com/ | en_AU |
local.type.status | Published Version | en_AU |
Downloads
Original bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- 1-s2.0-S0965174817301613-main.pdf
- Size:
- 539.03 KB
- Format:
- Adobe Portable Document Format
- Description: