Abstract
The ATP-binding cassette (ABC) transporters represent a superfamily of proteins that have important physiological roles in both prokaryotes and eukaryotes. In insects, ABC transporters have previously been implicated in insecticide resistance. The 91-R strain of Drosophila melanogaster has been intensely selected with DDT over six decades. A recent selective sweeps analysis of 91-R implicated the potential role of MDR49, an ABC transporter, in DDT resistance, however, to date the details of how MDR49 may play a role in resistance have not been elucidated. In this study, we investigated the impact of structural changes and an alternative splicing event in MDR49 on DDT-resistance in 91-R, as compared to the DDT susceptible strain 91-C. We observed three amino acid differences in MDR49 when 91-R was compared with 91-C, and only one isoform (MDR49B) was implicated in DDT resistance. A transgenic Drosophila strain containing the 91-R-MDR49B isoform had a significantly higher LD50 value as compared to the 91-C-MDR49B isoform at the early time points (6 h to 12 h) during DDT exposure. Our data support the hypothesis that the MDR49B isoform, with three amino acid mutations, plays a role in the early aspects of DDT resistance in 91-R.
Highlights
Post World War II, many agriculturally or medically important pests have been managed through the application of second-generation insecticides
ATP-binding Cassette (ABC) transporters are structurally characterized by four functional units: two highly conserved nucleotide-binding domains (NBDs), which are responsible for ATP-binding and hydrolysis, providing the energy for active transporting substrates across cellular membrane; and, two highly hydrophobic transmembrane domains (TMDs), which are involved in physical pathway for substrate translocation
We compared the sequences of the multidrug resistance 49 (MDR49), MDR50, and MDR65 genes between 91-R and 91-C to determine non-silent mutations within the ORFs that may lead to potential amino acid replacement
Summary
Post World War II, many agriculturally or medically important pests have been managed through the application of second-generation insecticides This form of selection pressure has led to the evolution of pesticide resistance in many of the target insect populations[1]. In the 91-R strain, constitutive over-expression of Cyp12d1, Cyp6a2 and Cyp6g1 have been observed[8,16,17], a recent selective sweeps analysis between 91-R and 91-C demonstrated that thirteen major and three minor effect chromosome intervals, with reduced nucleotide diversity, were identified only in the 91-R strain[18] Of these thirteen major and three minor loci, the only cytochrome P450 observed was Cyp4g1, which is thought to be associated with the reduced curricular penetration phenotype[19]. Unlike the NBDs, TMDs vary in sequence, length and helix number[22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
