Abstract
Aedes aegypti and Anopheles gambiae harbor the causative agents of diseases such as dengue fever and malaria, afflicting human morbidity and mortality worldwide. Given the worldwide emergence of resistance to insecticides, the current mainstay for vector control, identification of alternative modes of action for future insecticides is paramount. The serotonergic (5-HT) system has been documented to impact physiological mechanisms involved in disease transmission, suggesting its potential as a new mode of action target for future insecticide development. Target 5-HT receptors were cloned and expressed in the HEK293 cell line for functional and pharmacological characterization. Manipulation of the 5-HT system through microinjection of compounds suggests its involvement in the modulation of flight performance and blood-feeding behavior. By attenuating these two determinants of vectorial capacity, transmission and burden of disease could effectively be reduced. Considering these positive global health implications, the 5-HT system is a compelling target for the novel insecticide pipeline.
Highlights
Mosquitoes harbor multiple causative agents of diseases pertinent to global health
Putative 5-HT G-protein coupled receptors (GPCRs) genes were mined in VectorBase; eight Ae. aegypti and six An. gambiae genes were discovered to have distinct transcripts
Utilizing the An. gambiae Adipokinetic Hormone receptor protein (AGAP002156) as the outgroup, the 5-HT receptors were grouped into distinct clades, highlighting their respective subfamilies (Fig. 1)
Summary
Mosquitoes harbor multiple causative agents of diseases pertinent to global health. Aedes aegypti and Anopheles gambiae, transmit the parasite and arboviruses responsible for malaria, dengue, Zika, and chikungunya, afflicting high human morbidity and mortality worldwide. Given the current technology for generation sequencing, high-quality assemblies of arthropod genomes including Ae aegypti and An. gambiae have increased, facilitating the identification of GPCRs for functional and pharmacological investigation. Localization of the serotonin (5-HT) receptor family suggests its role in mediating processes important for disease transmission, including blood-feeding and locomotion, making this family of particular interest. Female Ae. aegypti and An. gambiae mosquitoes are predicted to take a blood meal every two to three days to ensure availability of proteins crucial for the egg development process[16]. Disruption to either of these physiological responses has the potential to negatively impact vectorial capacity and effectively reduce disease transmission and burden. As indirect determinants of vectorial competence, disrupting feeding and flight via the 5-HT receptor family could prove to be a new avenue and mode of action target for insecticide development
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