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Odour receptors and neurons for DEET and new insect repellents.

Kain P, Boyle SM, Tharadra SK, Guda T, Pham C, Dahanukar A, Ray A - Nature (2013)

Bottom Line: We tested several and found that most activate Ir40a(+) neurons and are repellents for Drosophila.The candidates contain chemicals that do not dissolve plastic, are affordable and smell mildly like grapes, with three considered safe in human foods.Our findings pave the way to discover new generations of repellents that will help fight deadly insect-borne diseases worldwide.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Entomology, University of California, Riverside, California 92521, USA [2].

ABSTRACT
There are major impediments to finding improved DEET alternatives because the receptors causing olfactory repellency are unknown, and new chemicals require exorbitant costs to determine safety for human use. Here we identify DEET-sensitive neurons in a pit-like structure in the Drosophila melanogaster antenna called the sacculus. They express a highly conserved receptor, Ir40a, and flies in which these neurons are silenced or Ir40a is knocked down lose avoidance to DEET. We used a computational structure-activity screen of >400,000 compounds that identified >100 natural compounds as candidate repellents. We tested several and found that most activate Ir40a(+) neurons and are repellents for Drosophila. These compounds are also strong repellents for mosquitoes. The candidates contain chemicals that do not dissolve plastic, are affordable and smell mildly like grapes, with three considered safe in human foods. Our findings pave the way to discover new generations of repellents that will help fight deadly insect-borne diseases worldwide.

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A new class of mosquito repellents with desirable safety profilesa, Arm-in-cage assay to measure repellency in mosquitoes. b, Mean percentage of female A. aegypti present for >5 sec on top net (Left=10% DEET, Right=solvent). Solvent controls performed separately (dark gray). c, Average time on net for each landing event in b. d, Mean percentage of female A. aegypti present for >5 sec on top net in non-contact assay. e, Cumulative repellency summed across minutes 2-5 of indicated non-contact treatment (10%) in comparison to appropriate solvent control. 40 mosquitoes/trial, n=5 trials/treatment for b,c,d, and e. f, Mean weight of vinyl pieces following submersion in indicated compounds for indicated amount of time. n=3, ***P < 10-5, Student's t-test. Error bars=S.E.M. g, Properties of new repellents. h, Model for DEET detection and processing in Drosophila.
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Figure 6: A new class of mosquito repellents with desirable safety profilesa, Arm-in-cage assay to measure repellency in mosquitoes. b, Mean percentage of female A. aegypti present for >5 sec on top net (Left=10% DEET, Right=solvent). Solvent controls performed separately (dark gray). c, Average time on net for each landing event in b. d, Mean percentage of female A. aegypti present for >5 sec on top net in non-contact assay. e, Cumulative repellency summed across minutes 2-5 of indicated non-contact treatment (10%) in comparison to appropriate solvent control. 40 mosquitoes/trial, n=5 trials/treatment for b,c,d, and e. f, Mean weight of vinyl pieces following submersion in indicated compounds for indicated amount of time. n=3, ***P < 10-5, Student's t-test. Error bars=S.E.M. g, Properties of new repellents. h, Model for DEET detection and processing in Drosophila.

Mentions: To test the effects of the identified chemicals on mosquito behaviour, we adapted a hand-in-glove assay that allows quantitative analysis of chemical repellency on mosquitoes attracted to a human arm (described in Supplementary Methods) (Fig. 6a, Supplementary Fig. 7). Female A. aegypti mosquitoes showed strong avoidance behaviour to DEET, irrespective of whether or not they could directly contact DEET (Fig. 6b). However, for sporadic landings the average time spent on the net before escape while not significant (p=0.203 for 10% DEET and p=0.06 for 1% DEET, Student's t-test) was reduced when direct contact with DEET was permitted, particularly at the lower concentrations (Fig. 6c). While it is difficult to asses from these experiments the direct contribution of the gustatory system alone, it demonstrates that mosquitoes can avoid DEET strongly at close range, even without making direct contact with it.


Odour receptors and neurons for DEET and new insect repellents.

Kain P, Boyle SM, Tharadra SK, Guda T, Pham C, Dahanukar A, Ray A - Nature (2013)

A new class of mosquito repellents with desirable safety profilesa, Arm-in-cage assay to measure repellency in mosquitoes. b, Mean percentage of female A. aegypti present for >5 sec on top net (Left=10% DEET, Right=solvent). Solvent controls performed separately (dark gray). c, Average time on net for each landing event in b. d, Mean percentage of female A. aegypti present for >5 sec on top net in non-contact assay. e, Cumulative repellency summed across minutes 2-5 of indicated non-contact treatment (10%) in comparison to appropriate solvent control. 40 mosquitoes/trial, n=5 trials/treatment for b,c,d, and e. f, Mean weight of vinyl pieces following submersion in indicated compounds for indicated amount of time. n=3, ***P < 10-5, Student's t-test. Error bars=S.E.M. g, Properties of new repellents. h, Model for DEET detection and processing in Drosophila.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3927149&req=5

Figure 6: A new class of mosquito repellents with desirable safety profilesa, Arm-in-cage assay to measure repellency in mosquitoes. b, Mean percentage of female A. aegypti present for >5 sec on top net (Left=10% DEET, Right=solvent). Solvent controls performed separately (dark gray). c, Average time on net for each landing event in b. d, Mean percentage of female A. aegypti present for >5 sec on top net in non-contact assay. e, Cumulative repellency summed across minutes 2-5 of indicated non-contact treatment (10%) in comparison to appropriate solvent control. 40 mosquitoes/trial, n=5 trials/treatment for b,c,d, and e. f, Mean weight of vinyl pieces following submersion in indicated compounds for indicated amount of time. n=3, ***P < 10-5, Student's t-test. Error bars=S.E.M. g, Properties of new repellents. h, Model for DEET detection and processing in Drosophila.
Mentions: To test the effects of the identified chemicals on mosquito behaviour, we adapted a hand-in-glove assay that allows quantitative analysis of chemical repellency on mosquitoes attracted to a human arm (described in Supplementary Methods) (Fig. 6a, Supplementary Fig. 7). Female A. aegypti mosquitoes showed strong avoidance behaviour to DEET, irrespective of whether or not they could directly contact DEET (Fig. 6b). However, for sporadic landings the average time spent on the net before escape while not significant (p=0.203 for 10% DEET and p=0.06 for 1% DEET, Student's t-test) was reduced when direct contact with DEET was permitted, particularly at the lower concentrations (Fig. 6c). While it is difficult to asses from these experiments the direct contribution of the gustatory system alone, it demonstrates that mosquitoes can avoid DEET strongly at close range, even without making direct contact with it.

Bottom Line: We tested several and found that most activate Ir40a(+) neurons and are repellents for Drosophila.The candidates contain chemicals that do not dissolve plastic, are affordable and smell mildly like grapes, with three considered safe in human foods.Our findings pave the way to discover new generations of repellents that will help fight deadly insect-borne diseases worldwide.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Entomology, University of California, Riverside, California 92521, USA [2].

ABSTRACT
There are major impediments to finding improved DEET alternatives because the receptors causing olfactory repellency are unknown, and new chemicals require exorbitant costs to determine safety for human use. Here we identify DEET-sensitive neurons in a pit-like structure in the Drosophila melanogaster antenna called the sacculus. They express a highly conserved receptor, Ir40a, and flies in which these neurons are silenced or Ir40a is knocked down lose avoidance to DEET. We used a computational structure-activity screen of >400,000 compounds that identified >100 natural compounds as candidate repellents. We tested several and found that most activate Ir40a(+) neurons and are repellents for Drosophila. These compounds are also strong repellents for mosquitoes. The candidates contain chemicals that do not dissolve plastic, are affordable and smell mildly like grapes, with three considered safe in human foods. Our findings pave the way to discover new generations of repellents that will help fight deadly insect-borne diseases worldwide.

Show MeSH
Related in: MedlinePlus