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Abamectin is metabolized by CYP392A16, a cytochrome P450 associated with high levels of acaricide resistance in Tetranychus urticae

Riga, M., Tsakireli, D., Ilias, A., Morou, E., Myridakis, A., Stephanou, E.G., Nauen, R., Dermauw, W., Van Leeuwen, T., Paine, Mark ORCID: and Vontas, John (2014) 'Abamectin is metabolized by CYP392A16, a cytochrome P450 associated with high levels of acaricide resistance in Tetranychus urticae'. Insect Biochemistry and Molecular Biology, Vol 46, pp. 43-53.

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Abamectin is one of the most important insecticides worldwide. It is used against major agricultural pests and insects of public health importance, as well as against endoparasites in animal health. Abamectin has been used successfully for the control of the spider mite Tetranychus urticae, a major agricultural pest with global distribution, an extremely diverse host range, and a remarkable ability to develop resistance against insecticides including abamectin. Target site resistance mutations may explain a large part of resistance, although genetic evidence and transcriptomic data indicated that additional mechanisms may also be implicated in the abamectin resistant phenotype.

To investigate a functional link between cytochrome P450-mediated metabolism and abamectin resistance, we recombinantly expressed three cytochrome P450s (CYP392A16, CYP392D8 and CYP392D10) that have been associated with high levels of abamectin resistance in a resistant T. urticae strain isolated from Greece. CYP392A16 was expressed predominately in its P450 form however, both CYP392D8 and CYP392D10 were expressed predominately as P420, despite optimization efforts on expression conditions.

CYP392A16 catalyses the hydroxylation of abamectin (Kcat = 0.54 pmol/min/pmol P450; Km = 45.9 μM), resulting in a substantially less toxic compound as confirmed by bioassays with the partially purified metabolite. However, CYP392A16 did not metabolize hexythiazox, clofentezine and bifenthrin, active ingredients that also showed reduced toxicity in the abamectin resistant strain. Among a number of fluorescent and luminescent substrates screened, Luciferin-ME EGE was preferentially metabolized by CYP392A16, and it may be a potential diagnostic probe for metabolic resistance detection and monitoring.

Item Type: Article
Subjects: QU Biochemistry > Enzymes > QU 135 Enzymes
QU Biochemistry > Cells and Genetics > QU 350 Cellular structures
QX Parasitology > Arthropods > QX 475 Sarcoptidae (Mites) (e.g., Sarcoptes scabiei)
WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by)
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):
Depositing User: Samantha Sheldrake
Date Deposited: 05 Sep 2014 09:15
Last Modified: 06 Feb 2018 13:07


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