Graphical Abstract Highlights d Ae. aegypti Ir8a mutant mosquitoes cannot sense lactic acid, a human sweat component d Attraction to humans and human odor is reduced in Ir8a mutant mosquitoes d Ae. aegypti IR8a pathway responds to human-odor cues during blood feeding d The Ir8a mutant host-seeking defect cannot be rescued by other olfactory receptors SUMMARY Mosquitoes use olfaction as a primary means of detecting their hosts. Previously, the functional ablation of a family of Aedes aegypti olfactory receptors, the odorant receptors (ORs), was not sufficient to reduce host seeking in the presence of carbon dioxide (CO 2 ).This suggests the olfactory receptors that remain, such as the ionotropic receptors (IRs), could play a significant role in host detection. To test this, we disrupted the Ir8a co-receptor in Ae. aegypti using CRISPR/Cas9. We found that Ir8a mutant female mosquitoes are not attracted to lactic acid, a behaviorally active component of human sweat, and they lack odor-evoked responses to acidic volatiles. The loss of Ir8a reduces mosquito attraction to humans and their odor. We show that the CO 2 -detection pathway is necessary but not sufficient for IR8a to detect human odor. Our study reveals that the IR8a pathway is crucial for an anthropophilic vector mosquito to effectively seek hosts.

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Highlights d Catnip is a broad-acting insect repellent d The repellency is mediated via iridoids such as nepetalactone d Catnip and nepetalactone activate select insect TRPA1 isoforms d TRPA1-deficient mosquitoes show no aversion to catnip

Geosmin is one of the most recognizable and common microbial smells on the planet. Some insects, like mosquitoes, require microbial-rich environments for their progeny, whereas for other insects such microbes may prove dangerous. In the vinegar fly Drosophila melanogaster, geosmin is decoded in a remarkably precise fashion and induces aversion, presumably signaling the presence of harmful microbes. We have here investigated the effect of geosmin on the behavior of the yellow fever mosquito Aedes aegypti. In contrast to flies, geosmin is not aversive in mosquitoes but stimulates egg-laying site selection. Female mosquitoes could associate geosmin with microbes, including cyanobacteria consumed by larvae, who also find geosmin -as well as geosmin producing cyanobacteria -attractive. Using in vivo multiphoton imaging from mosquitoes with pan-neural expression of the calcium reporter GCaMP6s, we show that Ae. aegypti code geosmin in a similar fashion to flies, i.e. with extreme sensitivity and with a high degree of selectivity. We further demonstrate that geosmin can be used as bait under field conditions, and finally we show that geosmin, which is both expensive and difficult to obtain, can be substituted by beetroot peel extract, providing a cheap and viable mean of mosquito control and surveillance in developing countries.

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