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Examining New Ways to Control Disease-Carrying Insects

Mosquitoes

Purdue researchers have developed a method to discover the next generation of insecticides based on specific insect genomes, or hereditary information encoded in DNA.

| February 2, 2012

WEST LAFAYETTE, Ind. - Purdue researchers are discovering the next generation of insecticides directed at disease-carrying insects like mosquitoes, ticks and tsetse flies, which could help professionals in the human health, veterinary and crop production sectors.

Catherine A. Hill, associate professor of entomology in the College of Agriculture, and Val J. Watts, professor of medicinal chemistry and molecular pharmacology in the College of Pharmacy, say vector insects - which carry and transmit infectious pathogens or parasites to other living organisms - are developing resistance to insecticides sprayed in the air or embedded in bed nets. The increased resistance makes insecticides less effective.

"The development of insecticide resistance threatens our ability to control insects that transmit diseases, like malaria and Lyme disease or parasites like heartworm, to human and animal populations in both developed and under-developed nations," Hill said. "The transmission of diseases becomes more widespread, which reduces quality of life, impacts mortality and puts enormous pressure on health-care professionals."

Hill's background in vector insect biology and Watts' specialization in molecular pharmacology led them to create an approach that focuses on specific insect genomes, or hereditary information encoded in insect DNA.
"The genome of most of these vector insects already is mapped out, and each is unique. We have used genomic approaches to identify key receptors, or molecules, found on a cell's surface, on these insects' central nervous systems," Watts said.

They began with receptors that are involved with feeding. When larvae of the Aedes aegypti mosquito mature, they carry and transmit infectious pathogens or parasites to other living organisms. Purdue researchers have developed a method to discover the next generation of insecticides based on specific insect genomes, or hereditary information encoded in DNA.

"Targeting these receptors leads either to killing the insect or stopping it from feeding, which is how pathogens and parasites are spread," Hill said.

Because the approach focuses on vector insects' DNA, insecticides created through this method may be safer for humans and non-targeted organisms like companion pets and non-vector insects like honey bees. They also may have less impact on the environment than other insecticides.

Hill's and Watts' research teams are revisiting drugs previously approved by the U.S. Food and Drug Administration to look for insecticidal effects. Their paper, "A 'Genome-to-Lead' Approach for Insecticide Discovery: Pharmacological Characterization and Screening of Aedes aegypti D1-like Dopamine Receptors," which appears in the peer-reviewed PLoS Neglected Tropical Diseases journal, identifies a commonly used antidepressant as a larvicide.

"Amitriptyline has been prescribed for more than 50 years, and we know human physiology handles it very well: physicians, pharmacists and nurses interact with it without personal protective equipment," Watts said. "But it kills larvae of the mosquito that spreads yellow fever and dengue fever in the tropical and subtropical regions of the world. There may be other FDA-approved drugs we didn't realize can also be insecticides."

The next steps to develop the genome-centric method are to explore other drugs through an in vivo assay to discover insecticidal or larvicidal properties and identify novel chemicals that affect the targeted receptor of disease-carrying insects. Hill and Watts also are looking to develop private-public partnerships to determine the most effective methods to deliver these insecticides.

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