2009 Annual Report
1a.Objectives (from AD-416)
Objective 1: Discover and develop next generation topical skin repellents, spatial repellents, contact irritants, and toxicants against mosquitoes and other arthropod disease vectors. Research toward this objective will primarily involve a consortium of military, government, academic, and private industry research groups using high throughput bioassays to test model compounds selected via computational chemistry from the large chemical library maintained by the BASF Corporation.
Objective 2: Develop new technology for preparation of fabrics having insect controlling and/or repelling properties. Repellent compounds will be covalently bonded to fabric polymers, and the resulting polymers will be tested to determine if repellent activity against mosquitoes is retained; if these derivatized polymers are repellent, then research will continue to optimize conditions required to produce insect repellent fabrics.
Objective 3: Identify the mechanisms underlying the activity of key mosquito repellents and attractants, and develop ways to exploit the mechanisms for commercial use. This objective will focus on state-of-the-art application of odorant binding protein (OBP) research by covalently bonding cloned mosquito OBPs to HPLC columns for use in screening natural product and synthetic chemical libraries for binding activity. Bound compounds will be identified and tested in conventional behavioral bioassays for activity against mosquitoes. Also, the mechanisms of action for selected compounds will be investigated electrophysiologically, including single cell recording experimentation to pinpoint the sites of receptors involved in the perception of bioactive compounds.
1b.Approach (from AD-416)
Discover and develop next generation topical skin repellents, spatial repellents, contact irritants, and toxicants against mosquitoes and other arthropod disease vectors.
Develop new technology for preparation of fabrics having insect controlling and/or repelling properties.
Identify the mechanisms underlying the activity of key mosquito repellents and attractants, and develop ways to exploit the mechanisms for commercial use.
The focus of our research is the discovery and development of methods to protect people from medically important insects and other blood-sucking arthropods that transmit disease agents or are a public health issue. Scientists have identified and tested new, fast-acting insecticides for public health use. These candidate pyrethroid-based compounds were shown to be effective against numerous resistance species of mosquitoes. An invention disclosure for a patent application entitled, ‘Identification of key ligand in the development of more effective deterrents and repellents of arthropod vectors,’ has been submitted. We believe that these compounds induce desirable toxic effects against vectors of disease pathogens in minutes due to their high vapor pressure.
Fundamental research involving the yellow fever mosquito, Aedes aegypti, demonstrated that specific receptors located in the antennae responded to odors produced by the host. This research provides a better understanding of the elements that affect mosquito attraction to a vertebrate host and will hopefully lead to novel methods of mosquito control.
Research with bed bugs revealed that the glands of immature bed bugs produce two compounds that have never been associated with these blood-sucking insects. Considered ‘alerting scents’ or alarm pheromones, these compounds comprised more than 15% of the gland’s composition, and they may be important in attractants and traps designed to monitor and control bed bugs. Additional research with bed bugs showed that adult males had a preference for harborages (hiding places) that were treated with an extract of immature shed skins. This research may also be valuable in designing traps and lures meant to control bed bugs.
Mosquito odorant receptor characterized. There is a need to develop newer, more effective methods to protect humans from blood-sucking insects, like mosquitoes. Methodologies were developed for cloning odorant receptors from mosquitoes and expression of the odorant receptors in the membranes of frog oocytes. Electrophysiological techniques were used to determine odorant receptor specificity. One odorant receptor responded specifically to one of two mirror image forms of a compound; this mirror image of the compound is an important attractant for blood feeding insects. This was the first mirror-image-specific odorant receptor discovered and characterized for an invertebrate. A better understanding of the elements that affect mosquito attraction will lead to the development of novel methods to control these blood-sucking insects.
Bed bug chemicals identified. The resurgence of bed bugs has led to the need of developing better forms of control. Several new controls methods designed to attract and trap bed bugs incorporate chemicals produced by bed bugs. We identified two new compounds from the glands of bed bugs that may be important in their chemical ecology. Incorporation of these new compounds into existing traps may increase a trap’s efficiency, thereby achieving better bed bug control.
New mosquito and tick repellent. Newer, safer, and more effective repellents are needed to repel blood-sucking arthropods. This accomplishment focuses on the discovery of a new mosquito and tick repellent from commercially available natural products as well as modified bicyclic monoterpenoids. It is expected that Frescolat, a commercial food ingredient, will be used without any health risk for this application by arthropod repellent industries.
Vogt, R. G., Miller, N. E., Litvack, R., Fandino, R. A., Sparks, J., Staples, J., Friedman, R. and Dickens, J. C. 2009. The insect SNMP gene family. Insect Biochemistry and Molecular Biology. 39(7):448-456.
Zhang, A., Wang, S., Klun, J.A., Carroll, J.F., and Debboun, M. 2009. Isolongifolenone: A natural sesquiterpene repellent of ticks and mosquitoes. Journal of Medical Entomology. 46(1):100-106. Available www.insectscience.org/9.41.
Polsomboon S., Grieco, J., Chauhan, K. R., Tanasinchayakul, S., Chareonviriyaphap T. 2008. Behavioral responses of catnip (Nepeta cataria L.) by two species of mosquitoes, Aedes aegypti (L.) and Anopheles harrisoni
Harbach and Manguin, in Thailand. Journal of the American Mosquito Control Association. 24(4):513–519.