Human sweat taste and contact-guided behavior in Aedes aegypti

PROJECT SUMMARY Mosquitoes are responsible for transmitting disease to hundreds of millions of people each year. Behavior- modification strategies have been major tools in surveillance and control efforts. A lot of attention has been devoted to elucidating and manipulating detection of thermosensory and olfactory cues that drive host-seeking behavior. However, a critical gap exists in our understanding of contact chemosensation in mosquito-host interactions, despite the fact that biting and blood feeding behaviors are crucial factors in driving disease transmission. After a mosquito has found a host, she lands on and examines the skin surface, and probes it with her stylets before initiating a blood meal. It is well known that the human skin surface is replete with chemicals, including those found in sweat. An understanding of whether human sweat cues can be sensed by the mosquito taste system, and if so, whether these cues activate behaviors that precede initiation of blood meals, would provide a valuable entry point for developing new behavior-modifying tools for surveillance and control. Our model of choice is Ae. aegypti, a vector of Dengue, Chikungunya, and Zika viruses, which is responsible for an enormous worldwide burden on human health, and is now also established in some regions of the United States. We propose to explore the hypothesis that soluble compounds present on human skin are sensed by the mosquito taste system and activate close-range behaviors that precede blood feeding. We focus on human sweat components, which include free amino acids in addition to salts, acids and ammonia derivatives. The premise behind our hypothesis is supported by our pilot data, in which we find that an artificial sweat mixture as well as certain individual amino acids and salt can activate taste neurons in female mosquitoes. Further, mixtures presented on a filter paper target can stimulate interaction and probing attempts in mated females. The specific goals of our proposal will be accomplished via two aims. In AIM 1, we will create a map of taste responsivity of human sweat components and mixtures in the female Aedes aegypti mosquito. We will determine if these stimuli promote residency or pre-feeding behaviors such as labellating and probing using independent population-based and single-female behavior assays. In AIM 2, we will evaluate whether cellular and behavioral responses to human sweat tastants are altered by knocking out selected taste receptors/co- receptors using CRISPR/Cas9-mediated genome editing. The results of the proposed studies will provide important molecular and neurophysiological insights into mosquito taste-guided behaviors elicited by compounds found in human sweat.