Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Sara A. Bickersmith
,
John D. Jurczynski
,
Maria Anice M. Sallum
ORCID logo ,
Leonardo Suveges Moreira Chaves
,
Eduardo S. Bergo
ORCID logo ,
Gloria A. D. Rodriguez
,
Clara A. Morante
,
Carlos T. Rios
,
Marlon P. Saavedra
,
Freddy Alava
,
Dionicia Gamboa
ORCID logo ,
Joseph M. Vinetz
ORCID logo ,
Jan E. Conn
*
Version 1 : Received: 31 August 2023 / Approved: 1 September 2023 / Online: 1 September 2023 (10:43:58 CEST)

A peer-reviewed article of this Preprint also exists.

Bickersmith, S.A.; Jurczynski, J.D.; Sallum, M.A.M.; Chaves, L.S.M.; Bergo, E.S.; Rodriguez, G.A.D.; Morante, C.A.; Rios, C.T.; Saavedra, M.P.; Alava, F.; Gamboa, D.; Vinetz, J.M.; Conn, J.E. 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. Genes 2023, 14, 1892. Bickersmith, S.A.; Jurczynski, J.D.; Sallum, M.A.M.; Chaves, L.S.M.; Bergo, E.S.; Rodriguez, G.A.D.; Morante, C.A.; Rios, C.T.; Saavedra, M.P.; Alava, F.; Gamboa, D.; Vinetz, J.M.; Conn, J.E. 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. Genes 2023, 14, 1892.

Abstract

Indoor residual spray (IRS), mainly employing pyrethroid insecticides, is the most common intervention to prevent 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 of amino acid leading to 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 2014-2021. 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 IR 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

Nyssorhynchus darlingi; insecticide resistance; Ace-1; VGSC; Brazil; Peru

Subject

Biology and Life Sciences, Ecology, Evolution, Behavior and Systematics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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