@article{cb577ddda6dc454c9146b4db66733c37,
title = "Commonly Used Insect Repellents Hide Human Odors from Anopheles Mosquitoes",
abstract = "The mode of action for most mosquito repellents is unknown. This is primarily due to the difficulty in monitoring how the mosquito olfactory system responds to repellent odors. Here, we used the Q-system of binary expression to enable activity-dependent Ca2+ imaging in olfactory neurons of the African malaria mosquito Anopheles coluzzii. This system allows neuronal responses to common insect repellents to be directly visualized in living mosquitoes from all olfactory organs, including the antenna. The synthetic repellents N,N-diethyl-meta-toluamide (DEET) and IR3535 did not activate Anopheles odorant receptor co-receptor (Orco)-expressing olfactory receptor neurons (ORNs) at any concentration, and picaridin weakly activated ORNs only at high concentrations. In contrast, natural repellents (i.e. lemongrass oil and eugenol) strongly activated small numbers of ORNs in the Anopheles mosquito antennae at low concentrations. We determined that DEET, IR3535, and picaridin decrease the response of Orco-expressing ORNs when these repellents are physically mixed with activating human-derived odorants. We present evidence that synthetic repellents may primarily exert their olfactory mode of action by decreasing the amount of volatile odorants reaching ORNs. These results suggest that synthetic repellents disruptively change the chemical profile of host scent signatures on the skin surface, rendering humans invisible to Anopheles mosquitoes.",
keywords = "Anopheles, DEET, GCaMP6, QF2, calcium imaging, human odorants, malaria mosquito, masking, olfaction, repellents",
author = "Ali Afify and Betz, {Joshua F.} and Olena Riabinina and Chlo{\'e} Lahond{\`e}re and Potter, {Christopher J.}",
note = "Funding Information: We thank C. McMeniman, D. Task, S. Maguire, and K. Robinson for mosquito technical support and for comments on the manuscript; Sophia Hager for assistance with imaging experiments; and Mark Wu for the use of his imaging camera. This work was supported by grants from the Department of Defense to C.J.P. (W81XWH-17-PRMRP) and from the NIH to C.J.P. (NIAID R01Al137078), and by a Johns Hopkins 2018 Catalyst Award to C.J.P. a Johns Hopkins Malaria Research Institute Pilot Fund to C.J.P. and a Johns Hopkins Malaria Research Institute Postdoctoral Fellowship to A.A. We thank the Johns Hopkins Malaria Research Institute, Bloomberg Philanthropies, and Virginia Tech Department of Biochemistry for their support. Conceptualization and Methodology, A.A. and C.J.P.; Investigation, A.A. and C.L.; Resources, O.R.; Formal Analysis and Visualization, A.A. J.F.B. and C.L.; Writing – Original Draft, A.A. C.L. and C.J.P.; Writing – Review & Editing, A.A. J.F.B. O.R. C.L. and C.J.P.; Supervision, C.J.P.; Funding Acquisition, C.J.P. The authors declare no competing interests. Funding Information: We thank C. McMeniman, D. Task, S. Maguire, and K. Robinson for mosquito technical support and for comments on the manuscript; Sophia Hager for assistance with imaging experiments; and Mark Wu for the use of his imaging camera. This work was supported by grants from the Department of Defense to C.J.P. ( W81XWH-17-PRMRP ) and from the NIH to C.J.P. ( NIAID R01Al137078 ), and by a Johns Hopkins 2018 Catalyst Award to C.J.P., a Johns Hopkins Malaria Research Institute Pilot Fund to C.J.P., and a Johns Hopkins Malaria Research Institute Postdoctoral Fellowship to A.A. We thank the Johns Hopkins Malaria Research Institute, Bloomberg Philanthropies , and Virginia Tech Department of Biochemistry for their support. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2019",
month = nov,
day = "4",
doi = "10.1016/j.cub.2019.09.007",
language = "English (US)",
volume = "29",
pages = "3669--3680.e5",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "21",
}