Pyrethroid resistance in the New World malaria vector Anopheles albimanus is mediated by cytochrome P450 CYP6P5

Kusimo, Michael O., Mackenzie-Impoinvil, Lucy, Ibrahim, SulaimanSadi, Muhammad, Abdullahi, Irving, Helen, Hearn, Jack ORCID: https://orcid.org/0000-0003-3358-4949 and Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 (2022) 'Pyrethroid resistance in the New World malaria vector Anopheles albimanus is mediated by cytochrome P450 CYP6P5'. Pesticide Biochemistry and Physiology, Vol 183, e105061.

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Abstract

Pyrethroid resistance in the malaria vector Anopheles albimanus presents an obstacle to malaria elimination in the Americas. Here, An. albimanus CYP6P5 (the most overexpressed P450 in a Peruvian population) was functionally characterized. Recombinant CYP6P5 metabolized the type II pyrethroids, deltamethrin and α cypermethrin with comparable affinities (KM of 3.3 μM ± 0.4 and 3.6 μM ± 0.5, respectively), but exhibited a 2.7-fold higher catalytic rate for α-cypermethrin (kcat of 6.02 min− 1 ± 0.2) versus deltamethrin (2.68 min− 1 ± 0.09). Timecourse assays revealed progressive depletion of the above pyrethroids with production of four HPLCdetectable metabolites. Low depletion was obtained with type I pyrethroid, permethrin. Transgenic expression in Drosophila melanogaster demonstrated that overexpression of CYP6P5 alone conferred type II pyrethroid resistance, with only 16% and 55.3% mortalities in flies exposed to 0.25% α-cypermethrin and 0.15% deltamethrin, respectively. Synergist bioassays using P450 inhibitor piperonylbutoxide significantly recovered susceptibility (mortality = 73.6%, p < 0.001) in synergized flies exposed to 4% piperonylbutoxide, plus 0.25% α-cypermethrin, compared to non-synergized flies (mortality = 4.9%). Moderate resistance was also observed towards 4% DDT. These findings established the preeminent role of CYP6P5 in metabolic resistance in An. albimanus, highlighting challenges associated with deployment of insecticide-based control tools in the Americas.

Item Type:	Article
Subjects:	QX Parasitology > Insects. Other Parasites > QX 515 Anopheles QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.pestbp.2022.105061
Depositing User:	Georgia Harrison
Date Deposited:	25 May 2022 10:27
Last Modified:	15 Jun 2023 13:37
URI:	https://archive.lstmed.ac.uk/id/eprint/20458

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