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Title
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The effect of silencing immunity related genes on longevity in the naturally occurring **Anopheles arabiensis** mosquito population of southwest Ethiopia
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Author
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Abstract
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| Background: Vector control remains the most important tool to tackle malaria, but it is now severely constrained by the spread of insecticide and behavioral resistance of mosquito populations. Therefore, the development of new vector control tools is crucial. Such novel tools include anti-mosquito vaccines and the release of genetically modified mosquitoes. Possible targets for a vaccine or effector gene are immunity related genes of the mosquito, as blocking their activity breaks the mosquito midgut homeostasis and reduces the mosquito lifespan to such an extent that malaria transmission no longer occurs. Methods: RNA interference mediated gene knock down was performed to assess the effect of silencing the midgut homeostasis immunity related regulators FN3D1, FN3D2, FN3D3, GPRGR9 and PGRPLC3 on the longevity of naturally occurring Anopheles arabiensis mosquito populations. The survival of gene-silenced mosquitoes was monitored and their midgut microbiota load was assessed using flow cytometry. We then further examined the stability of the gene silencing effect of FN3D1 in mosquitoes bred in different breeding circumstances, i.e., using water collected from three different mosquito breeding sites including Jimma, Asendabo and Wolkite. Results: In the first study, significantly higher mortality rates were observed for the FN3D1, FN3D3 and GPRGr9 gene silenced mosquitoes as compared to the control group injected with dsRNA, LacZ. The highest bacterial load ratios were observed for FN3D1 compared to the control gene LacZ, equal to 2.66. The mortality rates were reversed when the gene-silenced mosquitoes were treated with antibiotic mixtures indicating that the observed mortality was related with gut microbiota. In the second study we observed variation in different physicochemical parameters and water bacterial count between the sites. There was variation in adult survival of naïve mosquitoes (mosquitoes without gene silencing) between the sites, but the gene silencing effect was constant over the different sites, i.e., absence of interaction between site and silencing effect. Conclusion: We demonstrated that interfering with the expression of the FN3D1 genes causes a significant reduction of the longevity of naturally occurring An. arabiensis mosquitoes. Therefore, FN3D1 is a good candidate to develop mosquito life shortening malaria control tools either through host vaccination or transgenic approaches. Our further investigation on other arthropods including the sand fly shows that this approach could possibly be used to develop an integrated vaccine targeting both vectors. |
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Language
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English
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Publication
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Ghent
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Ghent University & Antwerp University
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2022
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Volume/pages
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xviii, 157 p.
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Full text (open access)
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