Abstract
Insecticide resistance in Aedes aegypti populations hinders vector control programs. Many studies have focused on the classical mechanisms, kdr mutations, and metabolic enzymes to understand the development of insecticide resistance. In this study, we subjected a strain of Ae. aegypti to selective pressure for 13 consecutive generations to understand the development and extent of insecticide resistance. We delved into the transcriptomics of this pressured strain to gain insights into the molecular changes underlying insecticide resistance in Ae. aegypti. Our data suggest mosquito resistance is influenced by additional mechanisms that are difficult to explain using only classical mechanisms. The response by mosquitoes varies depending on the exposure time. Initially, when mosquitoes are in contact with insecticides, they modulate the expression of metabolic enzymes and gain some point mutations in the sodium channel genes. After long-term exposure, the mosquitoes respond to insecticides by expressing different proteins involved in the cuticle, energetic metabolism, and synthesis of proteases. We propose a model that includes these novel mechanisms found after prolonged insecticide exposure, which work in conjunction with established mechanisms (kdr and metabolic resistance) but have a different timeline in terms of expression and appearance.