Impact of Increased AMP-Protein Kinase Activity on the Fitness, Metabolism and Pathogen Resistance of Anopheles Stephensi Mosquitoes

Abstract

Mosquitoes are known to transmit several pathogens that cause major human diseases in almost every part of the world. An example is malaria caused by the parasite belonging to the genus Plasmodium. Malaria causes high morbidity and mortality. Current vector control interventions have largely focused on targeting the adult mosquito through indoor residual spraying and insecticide-treated bed nets. However, these interventions are being threatened by the current increase in insecticide resistance, warranting the need to develop novel strategies for malaria control. One such strategy is to genetically modify mosquito vector, making them resistant to the malaria parasite to replace the wild population. Genes that enhance mitochondrial integrity and homeostasis are potential targets in improving mosquito fitness and anti-pathogen resistance, as they have been shown to regulate several life history traits in vertebrates and invertebrates. In this work, we generated a transgenic (TG) Anopheles stephensi mosquito line expressing active AMP protein kinase (AMPK), a key regulator of metabolism and mitochondrial homeostasis, specifically in the midgut and observed its impact on metabolism, lifespan, reproduction, and immunity. Although we observed no evidence of lifespan extension, we found that overexpression of AMPK resulted in a significant reduction of egg production and an enhanced Plasmodium falciparum parasite resistance in transgenic mosquitoes, as compared to the wildtype mosquitoes. Also, we observed a decrease in macronutrients 24 h after the mosquito consumed a blood meal. In summary, this work identifies midgut AMPK activity as an important regulator of metabolism, reproduction and innate immunity.