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. 2023 Sep 29;14(10):1892.
doi: 10.3390/genes14101892.

Mutations Linked to Insecticide Resistance Not Detected in the Ace-1 or VGSC Genes in Nyssorhynchus darlingi from Multiple Localities in Amazonian Brazil and Peru

Sara A Bickersmith  1 , John D Jurczynski  1   2 , Maria Anice Mureb Sallum  3 , Leonardo S M Chaves  3 , Eduardo S Bergo  4 , Gloria A D Rodriguez  5 , Clara A Morante  5 , Carlos T Rios  5 , Marlon P Saavedra  6 , Freddy Alava  7 , Dionicia Gamboa  6   8   9 , Joseph M Vinetz  6   8   10 , Jan E Conn  1   2
Affiliations

Mutations Linked to Insecticide Resistance Not Detected in the Ace-1 or VGSC Genes in Nyssorhynchus darlingi from Multiple Localities in Amazonian Brazil and Peru

Sara A Bickersmith et al. Genes (Basel). .

Abstract

Indoor residual spray (IRS), mainly employing pyrethroid insecticides, is the most common intervention for preventing malaria transmission in many regions of Latin America; the use of long-lasting insecticidal nets (LLINs) has been more limited. Knockdown resistance (kdr) is a well-characterized target-site resistance mechanism associated with pyrethroid and DDT resistance. Most mutations detected in acetylcholinesterase-1 (Ace-1) and voltage-gated sodium channel (VGSC) genes are non-synonymous, resulting in a change in amino acid, leading to the non-binding of the insecticide. In the present study, we analyzed target-site resistance in Nyssorhynchus darlingi, the primary malaria vector in the Amazon, in multiple malaria endemic localities. We screened 988 wild-caught specimens of Ny. darlingi from three localities in Amazonian Peru and four in Amazonian Brazil. Collections were conducted between 2014 and 2021. The criteria were Amazonian localities with a recent history as malaria hotspots, primary transmission by Ny. darlingi, and the use of both IRS and LLINs as interventions. Fragments of Ace-1 (456 bp) and VGSC (228 bp) were amplified, sequenced, and aligned with Ny. darlingi sequences available in GenBank. We detected only synonymous mutations in the frequently reported Ace-1 codon 280 known to confer resistance to organophosphates and carbamates, but detected three non-synonymous mutations in other regions of the gene. Similarly, no mutations linked to insecticide resistance were detected in the frequently reported codon (995) at the S6 segment of domain II of VGSC. The lack of genotypic detection of insecticide resistance mutations by sequencing the Ace-1 and VGSC genes from multiple Ny. darlingi populations in Brazil and Peru could be associated with low-intensity resistance, or possibly the main resistance mechanism is metabolic.

Keywords: Ace-1; Brazil; Nyssorhynchus darlingi; Peru; VGSC; insecticide resistance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Map of Ny. darlingi collection sites in Amazonian Peru (GAM: Gamitanacocha; ZUN: Zungarococha; and CAH: Cahuide) and Brazil (ML: Mâncio Lima; CS: Cruzeiro do Sul; HUM: Humaitá; and MO: Machadinho d’Oeste).
Figure 2
Figure 2
Alignment of DNA genotypes (V1-V9) and amino acid translations (below each DNA sequence) of the VGSC gene kdr region sequenced from Ny. darlingi collected in Peru and Brazil. Dots indicate no base or amino acid change from consensus sequence. Forward (F primer) and reverse primer (R primer) regions (green boxes), intron position (gray), and codon 995 (black box), associated with pyrethroid and DDT resistance are denoted (image obtained from Geneious version 2020.2 created by Biomatters).
Figure 3
Figure 3
Alignment of a subset of Ace-1 DNA genotypes and amino acid translations (below each DNA sequence) displaying non-synonymous mutations (blue lines) detected in Ny. darlingi samples sequenced from Peru and Brazil. Dots indicate no base or amino acid change from consensus sequence. Forward (F primer) and reverse primer (R primer) regions (green boxes) and codon 280 (black box), which is associated with organophosphate and carbamate resistance, are denoted (image obtained from Geneious version 2020.2 created by Biomatters).
See this image and copyright information in PMC

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