The female Anopheles gambiae mosquito is an extremely efficient vector for the malarial parasite Plasmodium falciparum and transmits this deadly disease to nearly 500 million people, causing nearly 750,000 deaths every year. Since the mosquito relies primarily on the sense of smell to find a human host, the olfactory system is a prime target for development of strategies to disrupt contact between mosquitoes and humans. Current methods of control that exploit the mosquito olfactory system such as repellents applied to the skin like DEET and CO2-traps are not useful for the population at risk due to high costs, inconvenience of direct skin applications, and bulk. The goal of this proposal is to identify affordable, convenient, and safe odor-based applications that can be used in small quantities to protect a spatial area such as an abode from Anopheles mosquitoes, and design low-cost lures for traps. One of the primary cues that mosquitoes use from a distance is CO2 present in exhaled breath. As the mosquito navigates closer using the CO2 plumes, it is also thought to be attracted to skin and sweat associated odors. In this proposal we focus on the CO2-sensing neuron of Anopheles gambiae as a target for development of odor-mediated behavior disruption strategies. For this purpose we have developed an array of powerful technologies that involve neurophysiology, chemical- informatics, and behavioral analysis. First, we plan to investigate a novel observation that the CO2-sensing neuron is also involved in detecting human-skin odorants, presumably causing close-range attraction. Since little is understood about attraction towards skin, we expect our analyses to reveal mechanisms underlying this important behavioral process. Second, we plan to identify odorants that can mimic the olfactory activity of CO2, and test their utility in acting as efficient lures for traps.And third, we propose to identify odorants that can block detection of CO2 by either inhibiting the CO2-sensing neuron, or by 'ultra-prolonged' activation of the neuron. These CO2-detection masking odors will be tested for the ability to protect a spatial area, such as a small abode, fromhost-seeking Anopheles mosquitoes. Successful completion of this proposal will provide safe and affordable odorants that can reduce contact between humans and Anopheles gambiae mosquitoes.

Public Health Relevance

Anopheles gambiae mosquitoes transmit malaria the most dangerous vector borne disease that infects ~500 million people worldwide, causing ~750,000 deaths every year. Malaria is anticipated to remain one of the major health problems globally due to a lack of vaccines, deterioration of public health infrastructures, and lack of effective control and surveillance methods for the vector in Africa. Methods that inhibit vector-human contact, such as insect repellents or traps, can play a critical role in controlling the spread of malaria if they were effective and affordable for widespread use. Successful completion of this proposal will lead to identification of safe and affordable odor molecules in the form of repellent and lures for traps that can block host-seeking mosquitoes from human contact by interfering with their CO2- sensing system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
High Priority, Short Term Project Award (R56)
Project #
1R56AI099778-01
Application #
8507822
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero, Adriana
Project Start
2012-08-01
Project End
2013-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$359,769
Indirect Cost
$109,769
Name
University of California Riverside
Department
Zoology
Type
Schools of Earth Sciences/Natur
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521
Webster, Ben; Lacey, Emerson S; Cardé, Ring T (2015) Waiting with bated breath: opportunistic orientation to human odor in the malaria mosquito, Anopheles gambiae, is modulated by minute changes in carbon dioxide concentration. J Chem Ecol 41:59-66
Lacey, Emerson S; Ray, Anandasankar; Cardé, Ring T (2014) Close encounters: contributions of carbon dioxide and human skin odour to finding and landing on a host in Aedes aegypti. Physiol Entomol 39:60-68
Tauxe, Genevieve M; MacWilliam, Dyan; Boyle, Sean Michael et al. (2013) Targeting a dual detector of skin and CO2 to modify mosquito host seeking. Cell 155:1365-79
Kain, Pinky; Boyle, Sean Michael; Tharadra, Sana Khalid et al. (2013) Odour receptors and neurons for DEET and new insect repellents. Nature 502:507-12