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Article

Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance

1
Advanced Testing Laboratory, Cincinnati, OH 45242, USA
2
Department of Entomology, University of Arizona, Tucson, AZ 85721, USA
3
Department of Health Sciences, ECPI University, Virginia Beach, VA 23462, USA
4
Department of Entomology, Plant Pathology and Nematology, University of Idaho, Moscow, ID 83844, USA
5
Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA
*
Author to whom correspondence should be addressed.
Genes 2021, 12(1), 119; https://doi.org/10.3390/genes12010119
Received: 30 December 2020 / Revised: 12 January 2021 / Accepted: 13 January 2021 / Published: 19 January 2021
(This article belongs to the Special Issue Evolutionary Genetics of Insect Innate Immunity)
Mitochondrial integrity and homeostasis in the midgut are key factors controlling mosquito fitness and anti-pathogen resistance. Targeting genes that regulate mitochondrial dynamics represents a potential strategy for limiting mosquito-borne diseases. AMP-activated protein kinase (AMPK) is a key cellular energy sensor found in nearly all eukaryotic cells. When activated, AMPK inhibits anabolic pathways that consume ATP and activates catabolic processes that synthesize ATP. In this study, we overexpressed a truncated and constitutively active α-subunit of AMPK under the control of the midgut-specific carboxypeptidase promotor in the midgut of female Anopheles stephensi. As expected, AMPK overexpression in homozygous transgenic mosquitoes was associated with changes in nutrient storage and metabolism, decreasing glycogen levels at 24 h post-blood feeding when transgene expression was maximal, and concurrently increasing circulating trehalose at the same time point. When transgenic lines were challenged with Plasmodium falciparum, we observed a significant decrease in the prevalence and intensity of infection relative to wild type controls. Surprisingly, we did not observe a significant difference in the survival of adult mosquitoes fed either sugar only or both sugar and bloodmeals throughout adult life. This may be due to the limited period that the transgene was activated before homeostasis was restored. However, we did observe a significant decrease in egg production, suggesting that manipulation of AMPK activity in the mosquito midgut resulted in the re-allocation of resources away from egg production. In summary, this work identifies midgut AMPK activity as an important regulator of metabolism, reproduction, and innate immunity in An. stephensi, a highly invasive and important malaria vector species. View Full-Text
Keywords: AMPK; Anopheles stephensi; midgut; Plasmodium falciparum; malaria; metabolism; reproduction AMPK; Anopheles stephensi; midgut; Plasmodium falciparum; malaria; metabolism; reproduction
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MDPI and ACS Style

Oringanje, C.; Delacruz, L.R.; Han, Y.; Luckhart, S.; Riehle, M.A. Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance. Genes 2021, 12, 119. https://doi.org/10.3390/genes12010119

AMA Style

Oringanje C, Delacruz LR, Han Y, Luckhart S, Riehle MA. Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance. Genes. 2021; 12(1):119. https://doi.org/10.3390/genes12010119

Chicago/Turabian Style

Oringanje, Chioma, Lillian R. Delacruz, Yunan Han, Shirley Luckhart, and Michael A. Riehle 2021. "Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance" Genes 12, no. 1: 119. https://doi.org/10.3390/genes12010119

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