Fig. 7

A proposed RNAi mode of action that impairs pyrethroid resistance. a Susceptible mosquitoes do not carry mutations that affect pyrethroid activity on the target VGSC (wild type VGSC in orange). The pyrethroid molecules bind to the VGSC and promote a constantly open state of the VGSC. This results in an increased influx of Na⁺ ions into the cell, causing repetitive impulses, exhaustion and eventually death. b Resistant mosquitoes carry mutated modified VGSC (mVGSC in green) with reduced interaction with pyrethroids (red colored “T”). Therefore, the toxic consequence of the insecticide is nullified when resistant mosquitoes are exposed to the pyrethroid concentration that effects the susceptible population. c RNAi decreases the mVGSC density and therefore the insecticide:target ratio is shifted when mosquitoes are exposed to pyrethroid concentrations that have no effect on resistant populations. This ratio alteration represents an increased pyrethroid molecule number per target. The elevated insecticide concentration makes up for its impaired interaction with the mVGSC target, leading to binding and the associated harmful effect (red dotted “T”)