Exome-wide association of deltamethrin resistance in Aedes aegypti from Mexico

Insect Mol Biol. 2019 Oct;28(5):591-604. doi: 10.1111/imb.12575. Epub 2019 Mar 13.

Abstract

Aedes aegypti is the major vector of a number of arboviruses that cause disease in humans. Without vaccines or pharmaceuticals, pyrethroid insecticides remain the major tool for public health protection. Pyrethroid resistance is now widespread. Replacement substitutions in the voltage-gated sodium channel (vgsc) that reduce the stability of pyrethroid binding account for most of the resistance, but metabolic mechanisms also inactivate pyrethroids. High-throughput sequencing and the A. aegypti L5 annotated physical map has allowed interrogation of the exome for genes and single-nucleotide polymorphisms associated with pyrethroid resistance. We exposed females of A. aegypti from Mexico to a deltamethrin discriminating dose to designate them as resistant (active after 1 h) or susceptible (knocked down with no recovery after 4 h). The vgsc on chromosome 3 had the highest association, followed by genes proximal to vgsc. We identified potential detoxification genes located singly (eg HPX8C) or within clusters in chromosome 2 [three esterase clusters, two of cytochrome P450 monooxygenases (CYP)] and chromosome 3 (one cluster of 16 CYP325 and seven CYP9 genes). Deltamethrin resistance in A. aegypti is associated with mutations in the vgsc gene and a large assortment of genes.

Keywords: Aedes aegypti; SNP association; deltamethrin resistance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aedes / drug effects
  • Aedes / genetics*
  • Aedes / metabolism
  • Animals
  • Cytochrome P-450 Enzyme System / genetics
  • Exome
  • Female
  • Inactivation, Metabolic / genetics
  • Insecticide Resistance / genetics*
  • Insecticides / pharmacology
  • Mexico
  • Nitriles / pharmacology*
  • Polymorphism, Single Nucleotide
  • Pyrethrins / pharmacology*
  • Voltage-Gated Sodium Channels / genetics
  • Voltage-Gated Sodium Channels / metabolism

Substances

  • Insecticides
  • Nitriles
  • Pyrethrins
  • Voltage-Gated Sodium Channels
  • decamethrin
  • Cytochrome P-450 Enzyme System