title: A brain-specific cytochrome P450 responsible for the majority of deltamethrin resistance in the QTC279 strain of Tribolium castaneum.
abstract: Cytochrome P450-mediated detoxification is one of the most important mechanisms involved in insecticide resistance. However, the molecular basis of this mechanism and the physiological functions of P450s associated with insecticide resistance remain largely unknown. Here, we exploited the functional genomics and reverse genetic approaches to identify and characterize a P450 gene responsible for the majority of deltamethrin resistance observed in the QTC279 strain of Tribolium castaneum. We used recently completed whole-genome sequence of T. castaneum to prepare custom microarrays and identified a P450 gene, CYP6BQ9, which showed more than a 200-fold higher expression in the deltamethrin-resistant QTC279 strain when compared with its expression in the deltamethrin-susceptible Lab-S strain. Functional studies using both double-strand RNA (dsRNA)-mediated knockdown in the expression of CYP6BQ9 and transgenic expression of CYP6BQ9 in Drosophila melanogaster showed that CYP6BQ9 confers deltamethrin resistance. Furthermore, CYP6BQ9 enzyme expressed in baculovirus metabolizes deltamethrin to 4-hydroxy deltamethrin. Strikingly, we also found that unlike many P450 genes involved in insecticide resistance that were reported previously, CYP6BQ9 is predominantly expressed in the brain, a part of the central nervous system (CNS) containing voltage-gated sodium channels targeted by deltamethrin. Taken together, the current studies on the brain-specific insect P450 involved in deltamethrin resistance shed new light on the understanding of the molecular basis and evolution of insecticide resistance.
authors.affiliation: Department of Entomology, College of Agriculture, University of Kentucky, Lexington, KY 40546, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhu
authors.forename: R
authors.initials: R
authors.lastname: Parthasarathy
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.forename: Katharina
authors.initials: K
authors.lastname: Woithe
authors.forename: Martin
authors.initials: M
authors.lastname: Kaussmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Nauen
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Harrison
authors.forename: Subba R
authors.initials: SR
authors.lastname: Palli
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D017344:Genes, Insect / Q000235:genetics; D007305:Insecticide Resistance / Q000187:drug effects* / Q000235:genetics; D008969:Molecular Sequence Data; D009570:Nitriles / Q000494:pharmacology*; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D011722:Pyrethrins / Q000378:metabolism / Q000494:pharmacology*; D034622:RNA Interference / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D014231:Tribolium / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics
chemical_list: D009570:Nitriles; D011722:Pyrethrins; D011994:Recombinant Proteins; C017180:decamethrin; D003577:Cytochrome P-450 Enzyme System
references.citation: Insect Mol Biol. 2005 Jan;14(1):69-77
references.pmid: 15663776
references.citation: Insect Mol Biol. 2000 Oct;9(5):441-9
references.pmid: 11029662
references.citation: Science. 2002 Sep 27;297(5590):2253-6
references.pmid: 12351787
references.citation: Nature. 1982 Feb 18;295(5850):601-3
references.pmid: 6276777
references.citation: BMC Physiol. 2008 Sep 25;8:18
references.pmid: 18817570
references.citation: Insect Biochem Mol Biol. 2007 May;37(5):512-9
references.pmid: 17456446
references.citation: PLoS Genet. 2008 Nov;4(11):e1000286
references.pmid: 19043575
references.citation: Curr Biol. 2002 Feb 5;12(3):R85-6
references.pmid: 11839285
references.citation: Neuropsychopharmacology. 2009 Feb;34(3):634-40
references.pmid: 18668033
references.citation: Genome Biol. 2008 Jan 17;9(1):R10
references.pmid: 18201385
references.citation: Insect Mol Biol. 2008 Feb;17(1):27-37
references.pmid: 18237282
references.citation: Invert Neurosci. 2007 Mar;7(1):17-30
references.pmid: 17206406
references.citation: Genome Res. 2009 Mar;19(3):452-9
references.pmid: 19196725
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5731-6
references.pmid: 19289821
references.citation: Arch Insect Biochem Physiol. 1998;37(1):57-63
references.pmid: 9397514
references.citation: Annu Rev Entomol. 2007;52:231-53
references.pmid: 16925478
references.citation: J Econ Entomol. 1998 Dec;91(6):1232-8
references.pmid: 9887680
references.citation: Insect Biochem Mol Biol. 2009 Oct;39(10):697-706
references.pmid: 19716416
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12807-12
references.pmid: 16120680
references.citation: Nature. 2008 Apr 24;452(7190):949-55
references.pmid: 18362917
references.citation: Genet Res. 2003 Dec;82(3):155-61
references.pmid: 15134194
references.citation: Genetics. 2007 Mar;175(3):1071-7
references.pmid: 17179088
references.citation: Biochem Biophys Res Commun. 2000 Jul 14;273(3):1132-7
references.pmid: 10891384
references.citation: Curr Drug Metab. 2001 Jun;2(2):199-214
references.pmid: 11469726