LAUSR

Simple Summary Pyrethroid-oriented vector control programs have increased worldwide to control adult Aedes aegypti mosquitoes and quell Aedes-borne disease epidemics. Due to years of pyrethroid use, resistance to pyrethroids in Ae. aegypti has become a global issue. In Florida, permethrin is the most common pyrethroid adulticide active ingredient used to control mosquito populations. Thus far, all wild Florida Ae. aegypti populations tested against permethrin have been found to be resistant. Metabolic resistance is a major mechanism of resistance in insects in which enzyme-mediated reactions cause the degradation or sequestration of insecticides. We performed assays to investigate the presence of metabolic resistance in 20 Florida Ae. aegypti populations and found that 11 populations (55%) exhibited metabolic resistance due to the action of at least one of three classes of metabolizing enzymes: oxidases, esterases, and glutathione transferases. Additionally, we identified two metabolic enzyme inhibitors: S.S.S-tributyl phosphorotrithioate (DEF; inhibits esterase activity) and diethyl maleate (DM; inhibits glutathione transferase activity), in addition to the commonly used piperonyl butoxide (PBO; inhibits oxidase activity), which were able to increase the efficacy of permethrin against resistant Ae. aegypti populations. Pre-exposure to DEF, PBO, and DM resulted in increased mortality after permethrin exposure in eight (73%), seven (64%), and six (55%) of the Ae. aegypti populations, respectively. Increasing the effectiveness of pyrethroids is important for mosquito control, as it is the primary method used for adult control during mosquito-borne disease outbreaks. Considering that DEF and DM performed similarly to PBO, they may be good candidates for inclusion in formulated pyrethroid products to increase their efficacy against resistant mosquitoes. Abstract Aedes aegypti is the principal mosquito vector for many arthropod-borne viruses (arboviruses) including dengue, chikungunya, and Zika. In the United States, excessive permethrin use has led to a high frequency of resistance in mosquitoes. Insecticide resistance is a significant obstacle in the struggle against vector-borne diseases. To help overcome metabolic resistance, synergists that inhibit specific metabolic enzymes can be added to formulated pyrethroid products. Using modified CDC bottle bioassays, we assessed the effect of three inhibitors (piperonyl butoxide (PBO), which inhibits oxidase activity; S.S.S-tributyl phosphorotrithioate (DEF), which inhibits esterase activity; and diethyl maleate (DM), which inhibits glutathione transferase activity) + permethrin. We performed these against 20 Florida Ae. aegypti populations, all of which were resistant to permethrin. Our data indicated that 11 out of 20 populations (55%) exhibited metabolic resistance. Results revealed 73% of these populations had significant increases in mortality attributed to DEF + permethrin, 64% to PBO + permethrin, and 55% to DM + permethrin compared to permethrin alone. Currently, PBO is the only metabolic enzyme inhibitor added to formulated pyrethroid products used for adult mosquito control. Our results suggest that the DEF and DM inhibitors could also be useful additives in permethrin products, especially against metabolically resistant Ae. aegypti mosquitoes. Moreover, metabolic assays should be conducted to better inform mosquito control programs for designing and implementing integrated vector management strategies.