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Genetics of Resistance to Malaria Parasites in the Mosquito Anopheles gambiae

Final Report Summary - MALARES (Genetics of Resistance to Malaria Parasites in the Mosquito Anopheles gambiae)

Malaria parasites are transmitted by mosquitoes of the genus Anopheles. Still, within a vector species, the ability of individual mosquitoes to support the development of parasites varies extensively, with some mosquitoes fully resistant to parasites, and therefore unable to transmit the disease. To dissect the genetic basis of mosquito resistance to malaria parasites, we have selected resistant and susceptible mosquito lines and performed genetic analyses. We further developed forward & reverse genetics tools to enable refined functional analyses in A. gambiae mosquitoes, including allele-specific RNA interference, improved transgenesis and gene editing.
Using these tools and a large collection of individual mosquitoes obtained from the genetic analyses and from field infections performed in Cameroon, we identified and characterized novel mosquito antiparasitic genes, including one whose polymorphism contributes to determine resistance. Notably, we demonstrated that overexpressing the resistant allele of a central antiparasitic gene failed to elevate mosquito resistance to parasite, thus suggesting that harnessing natural resistance genes in gene drive strategies to block parasite transmission might not be simple. Finally, we reported the transmission blocking properties of two new antiparasitic compounds. Our results provide a major contribution for the future development of novel malaria control strategies.