Variant Ionotropic Receptors in the Malaria Vector Mosquito Anopheles gambiae Tuned to Amines and Carboxylic Acids

Abstract

The principal Afrotropical human malaria vector mosquito, Anopheles gambiae, remains a significant threat to global health. A critical component in the transmission of malaria is the ability of An. gambiae females to detect and respond to human-derived chemical kairomones in their search for blood meal hosts. The basis for host odor responses resides in olfactory receptor neurons (ORNs) that express chemoreceptors encoded by large gene families, including the odorant receptors (ORs) and the variant ionotropic receptors (IRs). While ORs have been the focus of extensive investigation, functional IR complexes and the chemical compounds that activate them have not been identified in An. gambiae. Here we report the transcriptional profiles and functional characterization of three An. gambiae IR (AgIr) complexes that specifically respond to amines or carboxylic acids - two classes of semiochemicals that have been implicated in mediating host-seeking by adult females but are not known to activate An. gambiae ORs (AgOrs). Our results suggest that AgIrs play critical roles in the detection and behavioral responses to important classes of host odors that are underrepresented in the AgOr chemical space.

Not Just from Blood: Mosquito Nutrient Acquisition from Nectar Sources

“…aegypti orco mutants show impaired honey-seeking behavior compared with wild type controls, suggesting that nectar-foraging is mediated by the OR system [65]. IRs detect a wide range of volatiles, including amines, aldehydes, ketones, and carboxylic acids but their function in plant-related volatile detection remains unexplored [63,[66][67][68].…”

Aedes aegypti Mosquitoes Detect Acidic Volatiles Found in Human Odor Using the IR8a Pathway

“…aegypti and An. gambiae, human odors that elicit both electrophysiological and behavioral responses have been identified including ammonia, amines, carboxylic acids, lactic acid, ketones, sulfides, and 1-octen-3-ol [5][6][7][8][9][10].…”

Orthosteric muscarinic receptor activation by the insect repellent IR3535 opens new prospects in insecticide-based vector control

“…Modes of action of the most commonly used insect repellents such as DEET, IR3535, picaridine characterized so far are diverse. They can i) elicit deterrent feeding behavior, ii) modulate mosquito behavior through gustatory mechanism effect via gustatory receptor neurons 4,5 and iii) affect olfactory mechanism of action involving transmembrane odorant receptor proteins 6-8 located in olfactory receptor neurons [9][10][11][12][13][14][15][16][17] .Recent studies indicate that some repellent chemicals, such as DEET can also directly act on both insect peripheral and central nervous systems. They induce locomotor activity disruption, neuroexcitation (via octopamine receptors), cholinergic system alterations (e.g., acetylcholinesterase inhibition and M1/M3 muscarinic acetylcholine receptor subtype interactions) and monooxygenase regulation [17][18][19][20][21][22] .…”

“…Modes of action of the most commonly used insect repellents such as DEET, IR3535, picaridine characterized so far are diverse. They can i) elicit deterrent feeding behavior, ii) modulate mosquito behavior through gustatory mechanism effect via gustatory receptor neurons 4,5 and iii) affect olfactory mechanism of action involving transmembrane odorant receptor proteins 6-8 located in olfactory receptor neurons [9][10][11][12][13][14][15][16][17] .…”