Identifying the fitness costs of a pyrethroid-resistant genotype in the major arboviral vector Aedes aegypti

Abstract

Background: Effective vector control measures are essential in a world where many mosquito-borne diseases have no vaccines or drug therapies available. Insecticidal tools remain the mainstay of most vector-borne disease management programmes, although their use for both agricultural and public health purposes has resulted in selection for resistance. Despite this, little is known about the fitness costs associated with specific insecticide-resistant genotypes and their implications for the management of resistance. In Aedes aegypti, the primary vector of dengue, chikungunya, and Zika, the best-characterised resistance mechanisms are single-point mutations that protect the voltage-gated sodium channel from the action of pyrethroids. Methods: We evaluated the fitness cost of two co-occurring, homozygous mutations (V1016G and S989P) by backcrossing a resistant strain of A. aegypti from Timor-Leste into a fully susceptible strain from Queensland. The creation of the backcross strain allowed us to isolate these kdr mutations in an otherwise susceptible genetic background. Results: In comparison to the susceptible strain, the backcrossed colony exhibited longer larval development times (5 days, P < 0.001), 24% fewer mosquitoes reached the adult stage (P = 0.005), had smaller wing lengths (females, P = 0.019 and males, P = 0.007) and adult female mosquitoes had a shorter average lifespan (6 days, P < 0.0006). Conclusions: These results suggest specific and significant fitness costs associated with the double homozygous V1016G/S989P genotype in the absence of insecticides. The susceptibility of a population may recover if the fitness costs of resistant genotypes can be emphasised through the use of insecticide rotations and mosaics or the presence of untreated spatial or temporal refuges.

The presence of knockdown resistance mutations reduces male mating competitiveness in the major arbovirus vector, Aedes aegypti

“…We provide rare empirical evidence of behavioural changes associated with a specific double homozygous kdr genotype, isolated in a susceptible genomic background. Fitness comparisons between insecticide-resistant and susceptible mosquitoes often focus on life-history traits such as survival, development times and fecundity [ 13 – 15 ] and rarely use strains containing specific resistant genotypes in otherwise susceptible genetic backgrounds [ 15 , 21 ]. Here we used a backcrossed strain with a double homozygous, insecticide-resistance genotype (V1016G/S989P) isolated in a fully susceptible background [ 21 ] to explore the pleiotropic effect of these kdr mutations on behavioural traits.…”

“…aegypti . When considered alongside other reported fitness costs of insecticide resistance including adult survival, body size, fertility, fecundity and larval development times [ 14 , 15 , 21 , 34 ] it seems likely that susceptible mosquitoes, in the absence of insecticides, will have a major competitive advantage over resistant forms.…”

“…The derived backcross (R-BC) carries the homozygous mutations V1016G and S989P from the parental R-TL strain in a susceptible S-Cairns background. These kdr mutations are found in the same domain of the VGSC gene [ 10 ] and displayed complete linkage disequilibrium during the backcrossing process [ 21 ]. R-BC is resistant to DDT, permethrin, deltamethrin and lambda-cyhalothrin and susceptible to malathion and bendiocarb.…”

“…R-BC is resistant to DDT, permethrin, deltamethrin and lambda-cyhalothrin and susceptible to malathion and bendiocarb. The development of the R-BC strain and its genetic and phenotypic characterisation have already been described [ 21 ].…”

“…In mosquitoes, the causal relationship between kdr and its apparent pleiotropies are often equivocal because comparisons are commonly made between a small number of susceptible and resistant strains with poorly described genetic backgrounds. Studies that use backcrossing techniques [ 15 , 21 ] or careful genetic characterisation [ 18 ] to verify the precise impacts of kdr alleles are rare. Understanding and documenting the effects of kdr on mosquito behaviours such as mate-recognition and mating success, may be a key step in understanding how associated pleiotropies may assist remediation strategies aimed at reducing the frequency of resistant alleles and conserving pyrethroid susceptibility [ 22 , 23 ].…”