Various species of mosquitoes from the genus Anopheles vector the Plasmodium spp. parasites responsible for human malaria. While traditional, drug and insecticide based, efforts to control malaria have met with some success in limited geographic areas, there are still millions of cases each year and novel control strategies are needed to effect permanent reductions on a worldwide scale. One potential method to control malaria is to harness the mosquito immune system to create mosquitoes refractory to Plasmodium infection via genetic engineering. Efforts to create such mosquitoes have succeeded in multiple laboratories, but no such mosquitoes have been released as part of a large-scale malaria control program, partly due to a lack of knowledge about their biology. We undertook to expand our knowledge of the effects of genetic modification on An. stephensi mosquitoes. First, we characterized the transcriptomic and proteomic effects of transient up-regulation of the IMD pathway associated NF-kB transcription factor Rel2, showing that a very large number of both immune and non-immune genes are controlled by this up-regulation, and allowing us to identify novel anti-Plasmodium factors in the mosquito. We then measured the fitness of 5 genetically modified An. stephensi strains under a variety of conditions and using varied measures. These data showed that, while some genetically modified mosquitoes do bear a fitness cost due to the genetic modification, there is no inherent fitness cost to transgenesis. This indicates that genetically modified mosquitoes are a viable tool for malaria control and further efforts should pursue the testing of these mosquitoes on a larger scale in order to prepare them for use in global malaria control efforts.
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The effects of genetic modification on Anopheles stephensi
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