AeSCP-2 inhibitors (SCPIs) compete with cholesterol for binding to a mosquito sterol carrier protein-2 (AeSCP-2) known to aid in the uptake of cholesterol in mosquito cells. The larvicidal activities of AeSCP-2 inhibitor-1 (SCPI-1) and inhibitor-2 (SCPI-2) against Culex quinquefasciatus Say (Diptera: Culicidae) were therefore examined in insecticide-resistant Culex mosquitoes HAmCqG9, MAmCqG2, and BAmCqG0. All of the resistant Culex mosquito strains exhibited similar sensitivity to SCPI-1 and SCPI-2 inhibitors compared with a susceptible S-Lab strain. When an AeSCP-2 inhibitor was applied simultaneously with permethrin, the toxicity of permethrin to the second-instar larvae of all four strains of Culex mosquitoes increased, suggesting a synergistic effect of AeSCP-2 inhibitors on the toxicity of permethrin against Culex mosquitoes. Both SCPI-1 and SCPI-2 inhibitors caused a 2.4-to 3-fold reduction in the level of permethrin resistance in the highly resistant strain HAmCqG9. This result suggests that the mode of action of the AeSCP-2 inhibitors, which reduces the uptake of cholesterol by inhibiting the function of AeSCP-2 in mosquito cells, may interfere with the mechanisms or ability that govern permethrin resistance in the HAmCqG9 mosquito strain.
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