Dipteran insects act as vectors for a large number of human diseases. A major strategy for the control of insect pests is the use of insecticides, which have been enormously important over the last 50 years. Currently pyrethroids are one of the most widely used classes if 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 increased oxidative metabolism mediated by the cytochrome P450 microsomal monooxygenases. The 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. Our understanding of monooxygenase-mediated insecticide resistance has been limited because of the difficulty in isolating the individual P450s involved. CYP6D1 is the P450 responsible for high levels of monooxygenase mediated pyrethroid resistance in the LPR strain of house fly. CYP6D1-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 objective of the proposed research is to identify the CYP6D1 regulatory elements involved in insecticide resistance (i.e. those responsible for the increased transcription). The proposed research will provide an unprecedented understanding of the molecular basis of monooxygenase-mediated resistance in general, and CYP6D1-mediated pyrethroid resistance specifically. The ultimate goal of this research is to discover ways to delay the development of monooxygenase-mediated pyrethroid resistance.
