Specific signal pathway inhibition via oral dosage disrupts fecundity and fertility in Aedes aegypti

The yellow fever mosquito Aedes aegypti is a highly efficient vector of Dengue and Chickungunya viruses, filarid worms, and other pathogens that contribute to morbidity and mortality in both humans and animals.   Insecticides remain a prominent means of mosquito population control, but the spread of resistance to these chemicals necessitates the development of alternative chemicals and control measures. By hindering processes essential for reproduction in the female mosquito, such as blood meal digestion and egg development, the number of vectors may be decreased, and subsequently, so may disease transmission.   Here we explore the strategy of using chemical inhibitors to disrupt the convergent insulin and “target of rapamycin” (TOR) pathways, which stimulate and enhance different processes required for egg maturation in blood-fed Ae.aegypti.  Low doses of PQIP, an inhibitor of insulin receptor activation, and rapamycin, an inhibitor of the TOR protein, were fed in sugar solution to starved females.  Dosed and control females were tracked for mortality or allowed to blood feed and then their fecundity, fertility, and mortality were recorded.  We observed a reduction in fecundity with rapamycin, as well as, an inability to completely digest blood meals, but no effect on mortality.  However, no such effects were seen with PQIP.  The effect of rapamycin, coupled with the willingness of females to feed to the point of engorgement on the dosed sugar meal, supports its potential use as a component in toxic sugar baits.