Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding onPlasmodium-infected blood

Abstract

The introduction of genes that impair Plasmodium development into mosquito populations is a strategy being considered for malaria control. The effect of the transgene on mosquito fitness is a crucial parameter influencing the success of this approach. We have previously shown that anopheline mosquitoes expressing the SM1 peptide in the midgut lumen are impaired for transmission of Plasmodium berghei. Moreover, the transgenic mosquitoes had no noticeable fitness load compared with nontransgenic mosquitoes when fed on noninfected mice. Here we show that when fed on mice infected with P. berghei, these transgenic mosquitoes are more fit (higher fecundity and lower mortality) than sibling nontransgenic mosquitoes. In cage experiments, transgenic mosquitoes gradually replaced nontransgenics when mosquitoes were maintained on mice infected with gametocyte-producing parasites (strain ANKA 2.34) but not when maintained on mice infected with gametocyte-deficient parasites (strain ANKA 2.33). These findings suggest that when feeding on Plasmodium-infected blood, transgenic malaria-resistant mosquitoes have a selective advantage over nontransgenic mosquitoes. This fitness advantage has important implications for devising malaria control strategies by means of genetic modification of mosquitoes. malaria control ͉ genetic modification ͉ gene drive T he use of genetically modified mosquitoes refractory to pathogen transmission is a potential strategy for controlling vector-borne diseases (1-4). In the past few years, important technical advances, including germ-line transformation of mosquitoes, the characterization of tissue-specific promoters, and the identification of molecules that interfere with parasite development (effector molecules), have led to the generation of transgenic mosquitoes that are impaired in their capacity to transmit the malaria parasite (1, 5). However, although the feasibility of genetically modifying mosquito vector competence has been demonstrated in the laboratory, we do not yet know how transgenes can be introgressed into mosquito populations in the field. Several possible approaches have been proposed (transposable elements, Wolbachia, and meiotic drive), but success of any mechanism will depend in part on the fitness load that is imposed by the presence of the transgene.Previous studies suggested that transgenic mosquitoes are less fit than wild type (WT) (6, 7). Catteruccia et al. (6) found that Anopheles stephensi homozygous transgenic lines have lower fitness compared with WT, and Irvin et al. (7) reached similar conclusions with transgenic lines of Aedes aegypti. However, these studies could not distinguish fitness effects due to the transgene itself versus insertion-site effects and/or inbreeding depression (8). In a separate study, Moreira et al. (2) demonstrated that hemizygous transgenic mosquitoes expressing the SM1 dodecapeptide under the control of the blood-inducible carboxypeptidase promoter were as fit as WT controls when fed on blood of noninfected mice.Plasmodium and other path...

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