Mechanisms responsible for high levels of permethrin resistance in the house fly

The mechanisms responsible for > 6000-fold permethrin resistance in a pyrethroid-selected strain of house fly, Learn-PyR, were investigated. Through electrophysiological, in vitro metabolism, in vivo penetration and synergism studies it was demonstrated that the resistance mechanisms consisted of enhanced metabolic detoxification via the mixed-function oxidase (MFO) system, target-site insensitivity and decreased cuticular penetration. The major resistance mechanism was the MFO-mediated detoxification. The elevated MFO activity was correlated with higher levels of cytochrome P-450, cytochrome b₅ and NADPH-cytochrome c reductase activity. The kinetics of the latter showed similar K_m but greater V_max values in the Learn-PyR than in the susceptible strain, suggesting that the elevated activity was due to an altered amount, but not an altered form, of the enzyme. The Learn-PyR strain showed widely varying levels of resistance to the pyrethroids tested. Comparison of the pyrethroid structures with the resistance ratios revealed that resistance was highest in the presence of an unsubstituted phenoxybenzyl alcohol moiety. Substitution or certain modifications of the alcohol moiety reduced the level of resistance. Structure of the acid moiety or the presence or absence of an a-CN group did not affect the resistance level. These results are discussed with reference to the resistance mechanisms present.