A leucokinin mimic elicits aversive behavior in mosquito Aedes aegypti (L.) and inhibits the sugar taste neuron

Authors: KWAN, HYEOGSUN - Texas A&M University; AGHA, MOUTAZ - University Of Paris; SMITH, RYAN - Iowa State University; Nachman, Ronald; MARION-POLL, FREDERIC - University Of Paris; PETRANTONIO, PATRICIA - Texas A&M University

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/3/2016
Publication Date: 6/21/2016
Citation: Kwan, H., Agha, M.A., Smith, R.C., Nachman, R.J., Marion-Poll, F., Petrantonio, P.V. 2016. A leucokinin mimic elicits aversive behavior in mosquito Aedes aegypti (L.) and inhibits the sugar taste neuron. Proceedings of the National Academy of Sciences USA. 113(25):6880-6885.

Interpretive Summary: Insect pests have developed resistance to several conventional pesticides, and new approaches are needed for pest management. Although neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions, the neuropeptides hold little promise as pest control agents because they can be degraded in the target pest. New, selective control agents may be developed by designing mimics of these neuropeptides that resist degradation and either inhibit or over-stimulate critical neuropeptide-regulated life functions. We report on a discovery that in Aedes aegypti mosquitoes, which are important vectors of human disease, an ‘insect kinin’ neuropeptide receptor (active site) is expressed within taste hairs on the legs and mouthparts. A modified insect kinin version engineered to be resistant to degradation by insect pests, activates this insect kinin receptor with high potency, inhibiting sucrose taste detection directly at the level of the taste organs and eliciting a fast and highly aversive response in females during feeding. This novel discovery indicates that mosquito neuropeptide receptors could be new targets for discovering compounds to deter mosquitoes, preventing them from feeding in an environmentally-friendly fashion.

Technical Abstract: Insect kinins (leucokinins) are multifunctional peptides acting as neurohormones and neurotransmitters. In females of the mosquito vector Aedes aegypti (L.), aedeskinins are known to stimulate fluid secretion from the renal organs (Malpighian tubules) and hindgut contractions by activating a G protein-coupled kinin receptor designated Aedae-KR. We used protease-resistant kinin analogs (1728, 1729 and 1460) to evaluate their effects on sucrose perception and feeding behavior. In no-choice feeding bioassays (CAFE and plate assays) the analog 1728, which contains alpha-amino isobutyric acid (Aib), inhibited females feeding from sucrose. It further induced a quick fly-away or walk-away behavior following contact by the tarsi and the mouthparts. Electrophysiological recordings from single long labellar sensilla of the proboscis demonstrated that mixing the analog 1728 at 1mM with sucrose almost completely inhibited the detection of sucrose. Aedae-KR was immunolocalized in contact chemosensory neurons in prothoracic tarsi, and in sensory neurons and accessory cells of long labellar sensilla in the distal labellum. Silencing Aedae-KR by RNAi significantly reduced gene expression and eliminated the feeding aversion behavior resulting from contact with the analog 1728, directly implicating the Aedae-KR in the aversion response. This is the first report for any insect that kinin analogs modulate sucrose perception. The aversion to feeding elicited by analog 1728 suggests that synthetic molecules targeting the mosquito Aedae-KR in the labellum and tarsi should be investigated for the potential to discover novel feeding deterrents of mosquito vectors.