: Dipteran insects act as vectors for a large number of human diseases. Currently pyrethroids are one of the most widely used classes of insecticides for insect control. However, a major limitation with the use of insecticides for vector control is the development of resistance. An important mechanism by which insects become resistant to pyrethroid insecticides is through enhanced detoxification effected by increased activity of the cytochrome P450 microsomal monooxygenases. These monooxygenases are an extremely important metabolic system capable of metabolizing a wide range of compounds due to the presence of several different cytochrome P450 isoforms. CYP6D1 is the P450 responsible for high levels of monooxygenase-mediated pyrethroid resistance in the LPR strain of housefly. CYPGD1-mediated resistance is due to an elevated level of this protein in the resistant strain. The underlying basis for this elevated level is an increased rate of CYP6D1v1 transcription in the LPR strain. The objectives of the proposed research are 1) to identify the CYP6D1 regulatory elements involved in insecticide resistance (i.e., those responsible for the increased transcription) and 2) to examine if the different CYP6D1 alleles found in resistant and susceptible strains have a role in resistance. The proposed research will provide an unprecedented understanding of CYP6D1-mediated pyrethroid resistance specifically, and the molecular basis of monooxygenase-mediated resistance in general. The ultimate goal of this research is to discover ways to delay the development of monooxygenase-mediated pyrethroid resistance.
