Evaluating paratransgenesis using engineered symbiotic bacteria for Plasmodium inhibition in mosquito vectors: A systematic review

Malaria is one of the key world health problems, especially in sub-Saharan Africa, where the rising resistance to insecticides and antimalarial drugs is posing a threat to the current control mechanisms. New strategies are urgently needed to break the cycle of the spread of Plasmodium parasites by the Anopheles mosquito. A potential solution is paratransgenesis, which involves the genetic modification of naturally occurring mosquito-associated microbes to produce molecules that prevent the development of parasites in the gut of the mosquito. In this systematic review, we examined experimental studies that investigated paratransgenesis as a malaria control measure. Using the PRISMA guideline, we identified ten eligible studies that had engineered bacterial or fungal symbionts to express antiplasmodial effector proteins. These studies showed that feeding mosquitoes a sugar meal containing engineered microbes resulted in a stable colonization of the mosquito midgut. Several of the molecules tested were highly effective in reducing parasite development, with scorpine consistently showing strong transmission-blocking activity, achieving parasite inhibition rates greater than 90% in different experimental systems. Inhibitory effects were also further augmented by the combination of several effector molecules. Overall, the finding suggests that paratransgenesis has strong potential as an additional malaria control measure. Nevertheless, contests concerning ecological safety, microbial stability, and field implementation will need to be solved before large-scale implementation can be done.