Insulin and Target of Rapamycin pathway inhibition using novel reagents reduces fecundity of Aedes aegypti females in vivo

Currently, insecticides are the most common means of mosquito control.  However, increasing resistance to such compounds is becoming more prominent and complicating traditional means of control.  Resistance may be subverted, and perhaps even avoided, by targeting processes within the mosquito essential for blood meal digestion and reproduction.   The convergent insulin and target of rapamycin (TOR) pathways stimulate and enhance processes required for reproduction in female Ae. aegypti.  Blood fed female mosquitoes were injected with low doses of OSI906, an inhibitor of insulin receptor activation, or Torin 2, an inhibitor of the TOR protein.  Both of these reagents are currently in clinical trials as cancer treatment options.  Females were sampled at 48 hours for egg development.  Others were allowed to lay eggs and tracked for survival.  We observed a reduction in yolk deposition and egg production with both OSI906 and Torin 2.  These findings not only suggest the possibility of using cancer treatment drugs as a means of vector control due to the conserved nature of these two pathways, but also provide leads as to which reagents may be the most effective.