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RNA interference validation of detoxification genes involved in ivermectin tolerance in Drosophila melanogaster

Published on Oct 1, 2018in Insect Molecular Biology2.44
· DOI :10.1111/imb.12512
Ju Hyeon Kim7
Estimated H-index: 7
(UMass: University of Massachusetts Amherst),
J.A. Moreau1
Estimated H-index: 1
(UMass: University of Massachusetts Amherst)
+ 4 AuthorsJohn M. Clark26
Estimated H-index: 26
(UMass: University of Massachusetts Amherst)
Abstract
Previously, we observed increased transcription levels of specific cytochrome P450 monooxygenase (P450) and adenosine triphosphate binding cassette (ABC) transporter genes in human body lice, Pediculus humanus humanus, following exposure to ivermectin using the non‐invasive induction assay, which resulted in tolerance. To confirm the roles of these genes in induction and tolerance, the robust genetic model insect Drosophila melanogaster was chosen. Orthologous genes corresponding to the body louse P450 (Cyp9f2, Cyp6g2 and Cyp9h1) and ABC transporter (Mrp1, GC1824 as an ABCB type and CG3327 as an ABCG type) genes were selected for in vivo bioassay. Following a brief treatment with a sublethal dose of ivermectin, the mortality response was significantly slower, indicating the presence of tolerance. Concurrently, the transcription levels of Cyp9f2 and Mrp1 at 3 h and those of Cyp6g2, Cyp9h1, Mrp1, CG1824 and CG3327 at 6 h post‐treatment were upregulated, indicating gene induction. In behavioural bioassay using GAL4/UAS–RNA interference transgenic fly lines, increased susceptibility to ivermectin was observed following heat shock in the Cyp9f2 , Cyp6g2 , Cyp9h1 , Mrp1 or CG3327‐knockdown flies. Considering that these five genes are orthologous to those which had the largest over‐expression level following ivermectin‐induced tolerance in the body louse, the current results suggest that they are also associated with ivermectin detoxification in D. melanogaster and that body lice and D. melanogaster are likely to share, in part, similar mechanisms of tolerance to ivermectin.
  • References (34)
  • Citations (4)
References34
Newest
#1Nannan Liu (AU: Auburn University)H-Index: 29
#2Ming Li (AU: Auburn University)H-Index: 49
Last.Ting Li (AU: Auburn University)H-Index: 10
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#1Carlos J Chaccour (University of Navarra)H-Index: 10
#2Kevin C. Kobylinski (WRAIR: Walter Reed Army Institute of Research)H-Index: 12
Last.Brian D. Foy (CSU: Colorado State University)H-Index: 27
view all 7 authors...
#1Sié H PoodaH-Index: 1
#2Karine Mouline (IRD: Institut de recherche pour le développement)H-Index: 8
Last.Philippe Solano (IRD: Institut de recherche pour le développement)H-Index: 33
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Cited By4
Newest
#1Keon Mook Seong (MSU: Michigan State University)H-Index: 6
#2Brad S. Coates (ARS: Agricultural Research Service)H-Index: 23
Last.Barry Robert Pittendrigh (MSU: Michigan State University)H-Index: 32
view all 3 authors...
#1Shane Denecke (FORTH: Foundation for Research & Technology – Hellas)H-Index: 1
#2Luc SweversH-Index: 25
Last.John Vontas (FORTH: Foundation for Research & Technology – Hellas)H-Index: 42
view all 4 authors...
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