Anopheles gambiae is the main African mosquito vector of Plasmodium falciparum, the most deadly malaria parasite. Two paralogous genes, cpbAg1 and cpbAg2, coding for digestive carboxypeptidase B were previously identified, and CBPAg1 was shown to be involved in P. falciparum development and egg production in the mosquito (Lavazec et al., 2005; 2007). However, the possible role of CPBAg2 on these two phenotypes was not known. Our experimental work led first to demonstrate that CPBAg1 and CPBAg2 exhibit different biochemical characteristics. CPBAg1 is able to hydrolyse both basic residue lysine and arginine in contrast to CPBAg2 that is specific to arginine. Secondly, the kinetics of CPB synthesis in vivo show that CPBAg1 is produced early during the blood digestion process while CPBAg2 is produced all along this process. Lastly, using RNA interference to inactivate each or both cpbAg genes permitted to unravel the role of each CPBAg. CPBAg1 promotes P. falciparum development in the mosquito, suggesting a dependence of the sporogonic stages of the parasite for lysine. In contrast, CPBAg2 has a marginal effect on parasite development but act on egg development and maturation. Beside limiting egg maturation, the inactivation of cpbAg2 delays egg development. This physiological process seems to be dependent upon arginine availability produced mainly by CPBAg2. These results validate CPBAg1 and CPBA2 as targets for new strategies that will block the parasite within mosquitoes with a concomitant decrease in reproductive capacity, therefore targeting CPBAg1 and CPBA2 could contribute to reduce malaria transmission.
