Fitness costs of individual and combined pyrethroid resistance mechanisms, kdr and CYP-mediated detoxification, in Aedes aegypti

Background Aedes aegypti is an important vector of many human diseases and a serious threat to human health due to its wide geographic distribution and preference for human hosts. A. aegypti also has evolved widespread resistance to pyrethroids due to the extensive use of this insecticide class over the past decades. Mutations that cause insecticide resistance result in fitness costs in the absence of insecticides. The fitness costs of pyrethroid resistance mutations in A. aegypti are still poorly understood despite their implications for arbovirus transmission. Methodology/Principle findings We evaluated fitness based both on allele-competition and by measuring specific fitness components (i.e. life table and mating competition) to determine the costs of the different resistance mechanisms individually and in combination. We used four congenic A. aegypti strains: Rockefeller (ROCK) is susceptible to insecticides; KDR:ROCK (KR) contains only voltage-sensitive sodium channel (Vssc) mutations S989P+V1016G (kdr); CYP:ROCK (CR) contains only CYP-mediated resistance; and CYP+KDR:ROCK (CKR) contains both CYP-mediated resistance and kdr. The kdr allele frequency decreased over nine generations in the allele-competition study regardless of the presence of CYP-mediated resistance. Specific fitness costs were variable by strain and component measured. CR and CKR had a lower net reproductive rate (R0) than ROCK or KR, and KR was not different than ROCK. There was no correlation between the level of permethrin resistance conferred by the different mechanisms and their fitness cost ratio. We also found that CKR males had a reduced mating success relative to ROCK males when attempting to mate with ROCK females. Conclusions/Significance Both kdr and CYP-mediated resistance have a fitness cost affecting different physiological aspects of the mosquito. CYP-mediated resistance negatively affected adult longevity and mating competition, whereas the specific fitness costs of kdr remains elusive. Understanding fitness costs helps us determine whether and how quickly resistance will be lost after pesticide application has ceased.
Author summary Insecticides are still one of the most important tools, and often only tool, used to control disease vectors such as mosquitoes. The mosquito Aedes aegypti transmits several important pathogens impacting human health, including dengue and Zika viruses. Pyrethroid insecticides are commonly used to control A. aegypti in endemic areas, however, heavy use of insecticides has resulted in insecticide resistant mosquitoes. In A. aegypti, pyrethroid resistance evolved primarily through mutations in the pyrethroid target site (here referred to as kdr) and by increased detoxification by CYP enzymes. In this study, we sought to understand how these resistance modifications impact the mosquito fitness, since mutations often come with a biological cost. We found that both mechanisms have a cost and that they affect different aspects of mosquito physiology. CYP-mediated detoxification has a greater negative impact in the mosquito longevity and its ability to compete for mates. Kdr has a clear cost, but the specific function that is affected was neither reproduction nor longevity and therefore remains elusive. This study helps us understand how resistance influences mosquito life history traits and may help in the design of more targeted insecticide resistance management strategies.