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

Michael O Kusimo, Lucy Mackenzie-Impoinvil, Sulaiman S Ibrahim, Abdullahi Muhammad, Helen Irving, Jack Hearn, Audrey E Lenhart, Charles S Wondji

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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). Time-course assays revealed progressive depletion of the above pyrethroids with production of four HPLC-detectable 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.

Original languageEnglish
Article number105061
JournalPesticide Biochemistry and Physiology
Volume183
Early online date25 Feb 2022
DOIs
Publication statusPrint publication - May 2022
Externally publishedYes

Bibliographical note

Copyright © 2022. Published by Elsevier Inc.

Keywords

  • Animals
  • Anopheles/genetics
  • Cytochrome P-450 Enzyme System/genetics
  • Drosophila melanogaster/metabolism
  • Insecticide Resistance/genetics
  • Insecticides/metabolism
  • Malaria
  • Mosquito Control
  • Mosquito Vectors/genetics
  • Pyrethrins/metabolism
  • CYP6P5
  • Anopheles albimanus
  • Metabolic
  • α-Cypermethrin
  • Resistance

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