title: Resistance of Australian Helicoverpa armigera to fenvalerate is due to the chimeric P450 enzyme CYP337B3.
abstract: Worldwide, increasing numbers of insects have evolved resistance to a wide range of pesticides, which hampers their control in the field and, therefore, threatens agriculture. Members of the carboxylesterase and cytochrome P450 monooxygenase superfamilies are prominent candidates to confer metabolic resistance to pyrethroid insecticides. Both carboxylesterases and P450 enzymes have been shown to be involved in pyrethroid resistance in Australian Helicoverpa armigera, the noctuid species possessing by far the most reported resistance cases worldwide. However, specific enzymes responsible for pyrethroid resistance in field populations of this species have not yet been identified. Here, we show that the resistance toward fenvalerate in an Australian strain of H. armigera is due to a unique P450 enzyme, CYP337B3, which arose from unequal crossing-over between two parental P450 genes, resulting in a chimeric enzyme. CYP337B3 is capable of metabolizing fenvalerate into 4'-hydroxyfenvalerate, which exhibits no toxic effect on susceptible larvae; enzymes from the parental P450 genes showed no detectable fenvalerate metabolism. Furthermore, a polymorphic H. armigera strain could be bred into a susceptible line possessing the parental genes CYP337B1 and CYP337B2 and a resistant line possessing only CYP337B3. The exclusive presence of CYP337B3 in resistant insects of this strain confers a 42-fold resistance to fenvalerate. Thus, in addition to previously documented genetic mechanisms of resistance, recombination can also generate selectively advantageous variants, such as this chimeric P450 enzyme with an altered substrate specificity leading to a potent resistance mechanism.
authors.affiliation: Department of Entomology, Max Planck Institute for Chemical Ecology, Jena, Germany. nicole.joussen@gmx.de
authors.forename: Nicole
authors.initials: N
authors.lastname: Joußen
authors.forename: Sara
authors.initials: S
authors.lastname: Agnolet
authors.forename: Sybille
authors.initials: S
authors.lastname: Lorenz
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Schöne
authors.forename: Renate
authors.initials: R
authors.lastname: Ellinger
authors.forename: Bernd
authors.initials: B
authors.lastname: Schneider
authors.forename: David G
authors.initials: DG
authors.lastname: Heckel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000494:pharmacology*; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000939:Epitopes / Q000737:chemistry; D006418:Heme / Q000737:chemistry; D007306:Insecticides / Q000494:pharmacology; D007915:Lepidoptera / Q000187:drug effects* / Q000378:metabolism; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009570:Nitriles / Q000494:pharmacology*; D010571:Pest Control; D020033:Protein Isoforms; D011722:Pyrethrins / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D013696:Temperature
chemical_list: D004791:Enzyme Inhibitors; D000939:Epitopes; D007306:Insecticides; D009570:Nitriles; D020033:Protein Isoforms; D011722:Pyrethrins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; C017690:fenvalerate