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Protocols for Testing the Toxicity of Novel Insecticidal Chemistries to Mosquitoes
Published on: February 13, 2019
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High-content phenotypic screening identifies novel chemistries that disrupt mosquito activity and development
M V Murgia1, S Sharan1, J Kaur1
1Department Entomology, Purdue University, West Lafayette, IN 47907-2089, USA.
Pesticide Biochemistry and Physiology
|March 7, 2022
Summary
New high-content imaging screens identify novel chemical compounds for mosquito control. This approach aids in discovering new insecticides to combat insecticide-resistant mosquitoes and prevent vector-borne diseases.
Area of Science:
- Entomology and Vector Control
- Chemical Biology and Drug Discovery
- Public Health and Disease Prevention
Background:
- Insecticide resistance in mosquito populations necessitates the development of novel chemical agents.
- Vector-borne diseases (VBDs) pose a significant global health threat, requiring effective mosquito control strategies.
- Traditional insecticide discovery methods are being augmented by advanced screening technologies.
Purpose of the Study:
- To develop and implement an automated, high-throughput phenotypic screening (HTS) method for identifying new mosquito larvicides.
- To investigate novel chemical scaffolds with potential insecticidal activity against disease vectors like Aedes aegypti.
- To explore the utility of diverse entomological endpoints in assessing chemical efficacy beyond simple mortality.
Main Methods:
- Development of an automated HTS assay using high-content imaging of first instar (L1) Aedes aegypti larvae.
- Pilot screening of the Library of Pharmacologically Active Compounds (LOPAC1280) to identify active compounds.
- Secondary assays to evaluate the impact of selected compounds on larval activity, survival, and development.
Main Results:
- The HTS identified 92 compounds affecting larval activity and development, including known insecticides and modulators of mammalian targets like G protein-coupled receptors (GPCRs).
- Ritodrine hydrochloride reduced larval mobility but did not impact survival or development.
- Metergoline demonstrated dose-dependent effects, suppressing larval activity at high doses and causing pupal mortality at sub-lethal doses.
Conclusions:
- Phenotypic screening coupled with diverse entomological endpoints is a valuable approach for discovering novel insecticidal chemical scaffolds.
- The identified compounds, including GPCR modulators, represent potential starting points for new insecticide development.
- Understanding multi-modal efficacy spectra is crucial for effective vector control and VBD prevention strategies.
Keywords:
Active ingredientAedes aegyptiGPCRInsecticideLarvaeMode of actionMosquitoPhenotypic screening
