Emergence of hyper insecticide-resistant dengue vectors in Indochina Peninsula: threats of concomitant knockdown resistance mutations

• Published in: bioRxiv
• Main Authors: Kasai, Shinji, Itokawa, Kentaro, Uemura, Nozomi, Takaoka, Aki, Furutani, Shogo, Maekawa, Yoshihide, Kobayashi, Daisuke, Imanishi-Koayashi, Nozomi, Amoa-Bosompem, Michael, Murota, Katsunori, Higa, Yukiko, Kawada, Hitoshi, Minakawa, Noboru, Tran, Chi Cuong, Nguyen Thi Yen, Tran, Vu Phong, Sath Keo, Kang, Kroesna, Miura, Kozue, Ng, Lee Ching, Hwa-Jen Teng, Dadzie, Samuel, Subekti, Sri, Mulyatno, Kris Cahyo, Sawabe, Kyoko, Tomita, Takashi, Komagata, Osamu
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 07.03.2022; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: Aedes aegypti; Alleles; Dengue fever; Disease control; Haplotypes; Infectious diseases; Insecticides; Molecular modelling; Mutation; Neuroscience; Population genetics; Pyrethroids; Recombination; Sodium channels (voltage-gated); Vectors; Indochina; L982W; Leu982Trp; insecticide resistance
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2022.03.05.483084

Aedes aegypti (Linnaeus, 1762) is the main mosquito vector for dengue and other arboviral infectious diseases. Control of this important vector highly relies on the use of insecticides, especially pyrethroids. Nevertheless, the development of pyrethroid resistance is a major obstacle to mosquito/disease control worldwide. Here, we focused on the mutations in the target site of pyrethroid insecticides, voltage-sensitive sodium channel (Vssc), and found that Ae. aegypti collected from Vietnam has the L982W allele in the Vssc at a high frequency (>79%). L982W mutation is located in the highly conserved region of Vssc that is associated with sodium-ion selectivity and permeation rate. Strains having the L982W allele showed similar or even higher levels of resistance to pyrethroids than those having V1016G, a typical knockdown resistance allele in Asia. Furthermore, concomitant mutations L982W+F1534C and V1016G+F1534C were confirmed, and strains having these multiple Vssc mutations exhibited incomparably higher levels of pyrethroid resistance than any other field population ever reported. Molecular modeling analysis confirmed that these concomitant mutant alleles could interfere with approaching pyrethroid to Vssc. Remarkably, >90% of Vssc of Ae. aegypti were occupied by these hyper insecticide-resistant haplotypes in Phnom Penh city, Cambodia. Analysis of whole Vssc coding genes suggested that Vsscs have evolved into stronger resistant forms efficiently through gene recombination events. At this point, L982W has never been detected in Vssc of Ae. aegypti from any other neighboring countries. We strongly emphasize the need to be vigilant about these strong resistance genes spreading to the world through Indochina Peninsula. Competing Interest Statement The authors have declared no competing interest.