orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET.

Titleorco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET.
Publication TypeJournal Article
Year of Publication2013
AuthorsDeGennaro, M, McBride, CS, Seeholzer, L, Nakagawa, T, Dennis, EJ, Goldman, C, Jasinskiene, N, James, AA, Vosshall, LB
JournalNature
Volume498
Issue7455
Pagination487-91
Date Published2013 Jun 27
ISSN1476-4687
KeywordsAedes, Amino Acid Sequence, Animals, Base Sequence, DEET, Drug Resistance, Female, Genes, Insect, Honey, Host Specificity, Humans, Insect Repellents, Male, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutation, Neurons, Odorants, Olfactory Pathways, Volatilization
Abstract

<p>Female mosquitoes of some species are generalists and will blood-feed on a variety of vertebrate hosts, whereas others display marked host preference. Anopheles gambiae and Aedes aegypti have evolved a strong preference for humans, making them dangerously efficient vectors of malaria and Dengue haemorrhagic fever. Specific host odours probably drive this strong preference because other attractive cues, including body heat and exhaled carbon dioxide (CO2), are common to all warm-blooded hosts. Insects sense odours via several chemosensory receptor families, including the odorant receptors (ORs), membrane proteins that form heteromeric odour-gated ion channels comprising a variable ligand-selective subunit and an obligate co-receptor called Orco (ref. 6). Here we use zinc-finger nucleases to generate targeted mutations in the orco gene of A. aegypti to examine the contribution of Orco and the odorant receptor pathway to mosquito host selection and sensitivity to the insect repellent DEET (N,N-diethyl-meta-toluamide). orco mutant olfactory sensory neurons have greatly reduced spontaneous activity and lack odour-evoked responses. Behaviourally, orco mutant mosquitoes have severely reduced attraction to honey, an odour cue related to floral nectar, and do not respond to human scent in the absence of CO2. However, in the presence of CO2, female orco mutant mosquitoes retain strong attraction to both human and animal hosts, but no longer strongly prefer humans. orco mutant females are attracted to human hosts even in the presence of DEET, but are repelled upon contact, indicating that olfactory- and contact-mediated effects of DEET are mechanistically distinct. We conclude that the odorant receptor pathway is crucial for an anthropophilic vector mosquito to discriminate human from non-human hosts and to be effectively repelled by volatile DEET. </p>

DOI10.1038/nature12206
Alternate JournalNature
PubMed ID23719379
PubMed Central IDPMC3696029
Grant ListK99 DC012069 / DC / NIDCD NIH HHS / United States
R37 AI029746 / AI / NIAID NIH HHS / United States
R01 AI029746 / AI / NIAID NIH HHS / United States
AI29746 / AI / NIAID NIH HHS / United States
R00 DC012069 / DC / NIDCD NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
DC012069 / DC / NIDCD NIH HHS / United States