Basic studies on the insect cytochrome P450 for the development of new insecticides and synergistic agents.

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In order to seek novel target sites of insecticides or synergists, I studied on the mechanisms of insecticide resistance in vector mosquitoes, especially on the functional analysis of their cytochrome P450 monooxygenases. First of all, adult mosquitoes were selected in the laboratory with permethrin which is a class of pyrethroid insecticides. After the selections for 8 generations, the resistance level of mosquitoes (SPS8 strain) reached more than 1000-fold compared to an insecticide susceptible strain. Since permethrin susceptibility largely increased with pre-treatment of mosquitoes with piperonyl butoxide, it was suggested that cytochrome P450 monooxygenases have the major role in the resistance. In vitro metabolism study revealed that microsomal protein prepared from resistant mosquitoes catalyzed metabolism of ^<14>C-permethrin more rapidly to 4'HO-permethrin than that of a susceptible strain. Furthremore, permethrin hydroxylation activity was NADPH dependent and was strongly inhibited by piperonyl butoxide strongly suggested that cytochrome P450 monooxygenases are involved in permethrin resistance in SPS8 strain. The P450 isofoms which are associated with permethrin resistance are promising candidates as novel target sites of insecticides or synergists. Sodium channel gene was genotyped for 26 adult Aedes albopictus collected from Singapre in 2009. Surprisingly, more than 70% of mosquitoes possessed the knockdown resistance (kdr) gene. This is the first evidence for the presence of the kdr gene in Aedes albopictus and suggests the need to study the global distribution of this allele in this important vector insect.