- Email: [email protected]
Olfaction: Repellents that Congest the Mosquito Nose
Current Biology
Dispatches innervated by distinct nerves [19]. It will be fascinating to understand how all these different sensory inputs are represented on the genital cortex, how the development of the cortical maps is affected by sex hormones or behavioral manipulations, for example. Exciting times lie ahead in our understanding of this fundamental behavior.
REFERENCES 1. Sigl-Glo¨ckner, J., Maier, E., Takahashi, N., Sachdev, R., Larkum, M., and Brecht, M. (2019). Effects of sexual experience and puberty on mouse genital cortex revealed by chronic imaging. Curr. Biol. 29, 3588–3599. 2. Nummenmaa, L., Suvilehto, J.T., Glerean, E., Santtila, P., and Hietanen, J.K. (2016). Topography of human erogenous zones. Arch. Sex. Behav. 45, 1207–1216. 3. Di Noto, P.M., Newman, L., Wall, S., and Einstein, G. (2013). The hermunculus: what is known about the representation of the female body in the brain? Cereb. Cortex 23, 1005–1013. 4. Penfield, W., and Rasmussen, T. (1950). The Cerebral Cortex of Man: A Clinical Study of Localization of Function (New York: Macmillan).
5. Schott, G.D. (1993). Penfield’s homunculus: a note on cerebral cartography. J Neurol. Neurosurg. Psychiatry. 56, 329–333. 6. Farah, M.J. (1998). Why does the somatosensory homunculus have hands next to face and feet next to genitals? A hypothesis. Neural Comput. 10, 1983–1985. 7. Ramachandran, V.S., Rogers-Ramachandran, D., and Stewart, M. (1992). Perceptual correlates of massive cortical reorganization. Science 258, 1159–1160. 8. Kell, C.A., von Kriegstein, K., Rosler, A., Kleinschmidt, A., and Laufs, H. (2005). The sensory cortical representation of the human penis: revisiting somatotopy in the male homunculus. J. Neurosci. 25, 5984–5987. 9. Michels, L., Mehnert, U., Boy, S., Schurch, B., and Kollias, S. (2010). The somatosensory representation of the human clitoris: an fMRI study. Neuroimage 49, 177–184. 10. Lenschow, C., Copley, S., Gardiner, J.M., Talbot, Z.N., Vitenzon, A., and Brecht, M. (2016). Sexually monomorphic maps and dimorphic responses in rat genital cortex. Curr. Biol. 26, 106–113. 11. Lenschow, C., Sigl-Glo¨ckner, J., and Brecht, M. (2017). Development of rat female genital cortex and control of female puberty by sexual touch. PLoS Biol. 15, e2001283. 12. Lenschow, C., and Brecht, M. (2018). Physiological and anatomical outputs of rat genital cortex. Cereb. Cortex 28, 1472–1486.
13. Agmo, A., and Ellingsen, E. (2003). Relevance of non-human animal studies to the understanding of human sexuality. Scand. J. Psychol. 44, 293–301. 14. Wong-Riley, M. (1979). Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry. Brain Res. 171, 11–28. 15. Feldman, D.E., and Brecht, M. (2005). Map plasticity in somatosensory cortex. Science 310, 810–815. 16. Lauer, S.M., Lenschow, C., and Brecht, M. (2017). Sexually selected size differences and conserved sexual monomorphism of genital cortex. J. Comp. Neurol. 525, 2706–2718. 17. Takahata, T. (2016). What does cytochrome oxidase histochemistry represent in the visual cortex? Front. Neuroanat. 10, 79. 18. Madisen, L., Zwingman, T.A., Sunkin, S.M., Oh, S.W., Zariwala, H.A., Gu, H., Ng, L.L., Palmiter, R.D., Hawrylycz, M.J., Jones, A.R., et al. (2010). A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133–140. 19. Komisaruk, B.R., Wise, N., Frangos, E., Liu, W.C., Allen, K., and Brody, S. (2011). Women’s clitoris, vagina, and cervix mapped on the sensory cortex: fMRI evidence. J. Sex. Med. 8, 2822–2830.
Olfaction: Repellents that Congest the Mosquito Nose Jeffrey A. Riffell Department of Biology, University of Washington, Seattle, WA 98195, USA Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.09.053
How does the common insect repellent DEET modify a mosquito’s ability to detect humans? New research using GCaMP-expressing mosquitoes suggests that DEET works differently for different mosquito species. For An. coluzzii, DEET and other non-volatile repellents mask the mosquitoes’ ability to detect odors. But Odysseus said to the dear nurse Eurycleia: ‘‘Bring sulphur, old dame, to cleanse from pollution, and bring me fire, that I may purge the hall; and do thou bid Penelope come hither with her handmaidens, and order all the women in the house to come.’’ -Homer, Odyssey Chemical repellents for biting pests have long been used by our human ancestors
[1]. The active use of repellents has even been observed in our primate relatives, who crush millipedes and wipe the residue on their fur as a chemical defense against pests like mosquitoes [2,3]. Today, we luckily do not need to use fire and sulfur in our homes, or squash arthropods and wipe them in our hair. Instead, there are many different synthetic repellents available that reduce biting, including DEET, picaridin, and IR 3535 [4]. These repellents have two different modes for preventing bites: some repel
R1124 Current Biology 29, R1122–R1148, November 4, 2019 ª 2019 Elsevier Ltd.
pests at a distance [4,5], whereas others influence the pests once they land on the host [5,6]. In general, the best repellents do both. DEET, or N,N-diethyl-3methylbenzamide, is the ‘gold standard’ of repellents with its long-lasting repellency of diverse arthropod species, including mosquitoes, ticks, fleas and flies [4,7]. The chemical and physical properties of repellents, including DEET, are critical for their efficacy. DEET and its predecessor (N,N-diethylbenzamide) were engineered
Current Biology
Dispatches
D
EE
T
to have low volatility and thus remain at high concentrations on the users’ skin or clothes for extended periods. This is an important feature since highly volatile compounds will quickly evaporate and lose their efficacy over time. In the liquid phase, and once applied to the skin, these synthetic compounds will interact with the volatiles associated with the skin, thus altering and lowering emissions of these volatiles. Despite the efficacy of repellents like DEET, we know little about the molecular basis of how DEET impacts the mosquito’s sensory systems. In the yellow-fever mosquito (Aedes aegypti) and southern house mosquito (Culex quinquefasciatus), stimulation with DEET elicits antennal (electroantennogram) and olfactoryreceptor-neuron responses [5,8]. Mosquito olfactory-receptor neurons express odorant receptors and the odorant coreceptor, orco, which is critical for receptor functioning. In a seminal study, DeGennaro et al. [5] created mutations in orco of the yellow-fever mosquito and showed that orco mutants were insensitive to DEET, whereas wildtype mosquitoes still showed a reduction in attraction. In another important study, ectopic expression of the Cx. quinquefasciatus odorant receptor CquiOr136 in Xenopus oocytes revealed that this receptor was activated by DEET [9] and was responsible for mediating this mosquito’s aversive behavior to DEET [8]. These results, as well as how DEET lowers emission rates of skin volatiles, have given rise to three different hypotheses for how DEET modulates mosquito olfactory responses: DEET may activate a select number of odorant receptors to trigger repellency (so-called ‘smell and repel’ model); DEET may activate and inhibit many odorant receptors at once and therefore act as a ‘confusant’; and lastly, DEET may interfere with the detection of attractive odorants. Nonetheless, it remains unclear if DEET affects all mosquito species in the same manner, and whether all repellents have the same mode of action. Now, in this issue of Current Biology, Afify et al. [10] show that DEET masks attractive odors in the malaria-vector mosquito, Anopheles coluzzii, but only when DEET (or other repellents) are directly mixed with the odorants (like on the skin surface). To explore how
Skin surface
Figure 1. DEET’s suppression of odorant detection in An. coluzzii mosquitoes. In the liquid phase, and once applied to the surface of the skin, the non-volatile nature of certain repellents, like DEET, can reduce the emission of odorants from the skin and associated microbiota, making a person less attractive to foraging mosquitoes. However, research has also suggested that DEET may also operate as an odorant and repel mosquitoes from a distance. Afify et al. [10] demonstrate that for An. coluzzii mosquitoes, DEET suppresses the volatility of odorants, and that these mosquitoes are unable to detect DEET.
repellents modulate the detection of host odors, the authors created a transgenic An. coluzzii line that expresses the fluorescent calcium indicator GCaMP6f in olfactory sensory neurons. This was accomplished using the QF2/QUAS binary system, first developed by Potter and coworkers in Drosophila [11]. Afify and coworkers [10] used a transgenic mosquito that contained the regulatory genomic region for orco in An. coluzzii upstream of the sequence coding for the QF2 transcription factor. This method was first elegantly demonstrated by Riabinina et al. [12]. In tandem, the authors created a QUAS-GCaMP6f reporter line. When the mosquito lines are crossed, the QF2 is expressed, and it binds to the QUAS sequences, leading to expression of GCaMP6f in the orco-expressing neurons. The authors were thus able to functionally image the odor-evoked responses by olfactory receptor neurons on the mosquito olfactory appendages (the antennae, maxillary palps, and labella) and examine how repellents — both synthetic (picaridin, IR 3535, DEET), and natural (lemongrass, eugenol) — modulate those responses.
In contrast to the studies in Cx. quinquefasciatus or Ae. aegypti, Afify et al. [11] found that 100% DEET did not evoke calcium responses in the olfactory receptor neurons. Moreover, other synthetic repellents evoked either no response (IR 3535) or a very weak response (picaridin). However, both common odorants and natural repellents, like lemongrass oil or eugenol, evoked strong olfactory-receptor-neuron responses. How then do DEET and other repellents impact An. coluzzii biting preferences? In a series of carefully controlled experiments, the authors found that DEET masks odorants if they are mixed in the liquid phase. By contrast, if DEET is kept separate from the odorants, but co-released in the air at the same time as the odorants, then the masking effect is lost, and olfactory receptor neurons respond to the odorants similarly to when DEET is absent (Figure 1). Using a photoionization detector — which qualitatively measures the volatiles in the air — the authors were able to verify that the repellents lowered the volatility of odorants, thereby decreasing the concentration reaching the antennae. The
Current Biology 29, R1122–R1148, November 4, 2019 R1125
Current Biology
Dispatches authors were thus able to demonstrate that repellents can have multiple modes of action. On one hand, repellents like lemongrass may activate multiple types of olfactory receptor neurons, leading to a confusant effect in the mosquito, and on the other hand, DEET or any other nonvolatile repellent may suppress the volatile emissions from the skin, making it more difficult for An. coluzzii mosquitoes to detect us (Figure 1). This work has important implications for repellent design, but also raises questions for why some mosquito species detect DEET, but not others. First, there is arguably a need for new repellents that are non-toxic and can alter the skin’s odor to make it functionally non-attractive to mosquitoes. Using non-volatile compounds to suppress the volatility of odorants from the skin microbiota — thereby potentially rendering an individual olfactorily invisible to the mosquito — could be an important avenue to explore for interventions to prevent biting by An. coluzzii, a primary malaria vector in many regions of Africa. Afify et al. [11] also raise the question of how and why DEET differentially affects other mosquito species, or other biting pests. In Ae. aegypti and Cx. quinquefasciatus, research has suggested that DEET activates olfactory receptor neurons to operate as a spatial repellent, and DEET has been hypothesized to mimic natural plant-defensive compounds, like methyl jasmonate [10]. Examining the functional and genetic differences in the olfactory receptors between mosquito species could shed light on how DEET is detected and transduced by olfactory receptor neurons. Moreover, across insects, olfactory receptors are extremely diverse and relate to the ecology and evolutionary history of the insect species. Thus, it’s perhaps not surprising that DEET may function as an odorant for some insects, but not others. Another critical point to recognize is that DEET also acts as a contact repellent, potentially activating the touch or taste receptors located on the mosquito tarsae [6,13]. This contact repellency could explain the broad efficacy of DEET and related repellents across other biting pests, like flies, or even ticks, which lack orco and olfactory receptors. Future work will be needed to examine how repellents like DEET influence other sensory channels in
mosquitoes, like touch, taste, or other chemosensory receptors. Nonetheless, the authors’ development of the QF2/ QUAS binary expression system in mosquitoes provides exciting opportunities to explore these sensory channels, as well as other biological processes that can be leveraged for the control of human-disease vectors. REFERENCES 1. Herodotus. (1996 reprint). The Histories (London: Penguin).
repelled by volatile DEET. Nature 498, 487–491. 6. Dennis, E.J., Goldman, O.V., and Vosshall, L.B. (2019). Aedes aegypti mosquitoes use their legs to sense DEET on contact. Curr. Biol. 29, 1551–1556. 7. DeGennaro, M. (2015). The mysterious multimodal repellency of DEET. Fly 9, 45–51. 8. Syed, Z., and Leal, W.S. (2008). Mosquitoes smell and avoid the insect repellent DEET. Proc. Natl. Acad. Sci. USA 105, 13598–13603. 9. Xu, P., Choo, Y.M., De La Rosa, A., and Leal, W.S. (2014). Mosquito odorant receptor for DEET and methyl jasmonate. Proc. Natl. Acad. Sci. USA 111, 16592–16597.
2. Valderrama, X., Robinson, J.G., Attygalle, A.B., and Eisner, T. (2000). Seasonal anointment with millipedes in a wild primate: a chemical defense against insects? J. Chem. Ecol. 26, 2781–2790.
10. Afify, A., Betz, J.F., Riabinina, O., Lahonde`re, C., and Potter, C.J. (2019). Commonly used insect repellents hide human odors from Anopheles mosquitoes. Curr. Biol. 29, 3669– 3680.
3. Weldon, P.J., Aldrich, J.R., Klun, J.A., Oliver, J.E., and Debboun, M. (2003). Benzoquinones from millipedes deter mosquitoes and elicit self-anointing in capuchin monkeys (Cebus spp.). Naturwissenschaften 90, 301–304.
11. Potter, C.J., Tasic, B., Russler, E.V., Liang, L., and Luo, L. (2010). The Q system: a repressible binary system for transgene expression, lineage tracing, and mosaic analysis. Cell 141, 536–548.
4. Leal, W.S. (2014). The enigmatic reception of DEET— the gold standard of insect repellents. Curr. Opin. Insect. Sci. 6, 93–98.
12. Riabinina, O., Task, D., Marr, E., Lin, C.C., Alford, R., O’brochta, D.A., and Potter, C.J. (2016). Organization of olfactory centres in the malaria mosquito Anopheles gambiae. Nat. Commun. 7, 13010.
5. DeGennaro, M., McBride, C.S., Seeholzer, L., Nakagawa, T., Dennis, E.J., Goldman, C., Jasinskiene, N., James, A.A., and Vosshall, L.B. (2013). orco mutant mosquitoes lose strong preference for humans and are not
13. Lee, Y., Kim, S.H., and Montell, C. (2010). Avoiding DEET through insect gustatory receptors. Neuron 67, 555–561.
Termite Evolution: A Primal Knock on Wood or a Hearty Mouthful of Dirt Michael S. Engel Division of Entomology, Natural History Museum, and Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence, KS 66045, USA Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.09.016
Termite success is inexorably linked to their diet and symbiotic cellulolytic intestinal microorganisms. A new study reveals that soil feeding may have triggered a turnover in intestinal symbionts, rather than ectosymbiont cultivation, allowing termites to achieve ecological dominance. The link between wood consumption and the ecological success of termites is axiomatic. It is a universally acknowledged truth that the appearance
R1126 Current Biology 29, R1122–R1148, November 4, 2019 ª 2019 Elsevier Ltd.
of termites (infraorder Isoptera) from amongst the roaches (order Blattaria) was made possible by the integration of protistan endosymbionts, thus permitting
Dispatches innervated by distinct nerves [19]. It will be fascinating to understand how all these different sensory inputs are represented on the genital cortex, how the development of the cortical maps is affected by sex hormones or behavioral manipulations, for example. Exciting times lie ahead in our understanding of this fundamental behavior.
REFERENCES 1. Sigl-Glo¨ckner, J., Maier, E., Takahashi, N., Sachdev, R., Larkum, M., and Brecht, M. (2019). Effects of sexual experience and puberty on mouse genital cortex revealed by chronic imaging. Curr. Biol. 29, 3588–3599. 2. Nummenmaa, L., Suvilehto, J.T., Glerean, E., Santtila, P., and Hietanen, J.K. (2016). Topography of human erogenous zones. Arch. Sex. Behav. 45, 1207–1216. 3. Di Noto, P.M., Newman, L., Wall, S., and Einstein, G. (2013). The hermunculus: what is known about the representation of the female body in the brain? Cereb. Cortex 23, 1005–1013. 4. Penfield, W., and Rasmussen, T. (1950). The Cerebral Cortex of Man: A Clinical Study of Localization of Function (New York: Macmillan).
5. Schott, G.D. (1993). Penfield’s homunculus: a note on cerebral cartography. J Neurol. Neurosurg. Psychiatry. 56, 329–333. 6. Farah, M.J. (1998). Why does the somatosensory homunculus have hands next to face and feet next to genitals? A hypothesis. Neural Comput. 10, 1983–1985. 7. Ramachandran, V.S., Rogers-Ramachandran, D., and Stewart, M. (1992). Perceptual correlates of massive cortical reorganization. Science 258, 1159–1160. 8. Kell, C.A., von Kriegstein, K., Rosler, A., Kleinschmidt, A., and Laufs, H. (2005). The sensory cortical representation of the human penis: revisiting somatotopy in the male homunculus. J. Neurosci. 25, 5984–5987. 9. Michels, L., Mehnert, U., Boy, S., Schurch, B., and Kollias, S. (2010). The somatosensory representation of the human clitoris: an fMRI study. Neuroimage 49, 177–184. 10. Lenschow, C., Copley, S., Gardiner, J.M., Talbot, Z.N., Vitenzon, A., and Brecht, M. (2016). Sexually monomorphic maps and dimorphic responses in rat genital cortex. Curr. Biol. 26, 106–113. 11. Lenschow, C., Sigl-Glo¨ckner, J., and Brecht, M. (2017). Development of rat female genital cortex and control of female puberty by sexual touch. PLoS Biol. 15, e2001283. 12. Lenschow, C., and Brecht, M. (2018). Physiological and anatomical outputs of rat genital cortex. Cereb. Cortex 28, 1472–1486.
13. Agmo, A., and Ellingsen, E. (2003). Relevance of non-human animal studies to the understanding of human sexuality. Scand. J. Psychol. 44, 293–301. 14. Wong-Riley, M. (1979). Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry. Brain Res. 171, 11–28. 15. Feldman, D.E., and Brecht, M. (2005). Map plasticity in somatosensory cortex. Science 310, 810–815. 16. Lauer, S.M., Lenschow, C., and Brecht, M. (2017). Sexually selected size differences and conserved sexual monomorphism of genital cortex. J. Comp. Neurol. 525, 2706–2718. 17. Takahata, T. (2016). What does cytochrome oxidase histochemistry represent in the visual cortex? Front. Neuroanat. 10, 79. 18. Madisen, L., Zwingman, T.A., Sunkin, S.M., Oh, S.W., Zariwala, H.A., Gu, H., Ng, L.L., Palmiter, R.D., Hawrylycz, M.J., Jones, A.R., et al. (2010). A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133–140. 19. Komisaruk, B.R., Wise, N., Frangos, E., Liu, W.C., Allen, K., and Brody, S. (2011). Women’s clitoris, vagina, and cervix mapped on the sensory cortex: fMRI evidence. J. Sex. Med. 8, 2822–2830.
Olfaction: Repellents that Congest the Mosquito Nose Jeffrey A. Riffell Department of Biology, University of Washington, Seattle, WA 98195, USA Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.09.053
How does the common insect repellent DEET modify a mosquito’s ability to detect humans? New research using GCaMP-expressing mosquitoes suggests that DEET works differently for different mosquito species. For An. coluzzii, DEET and other non-volatile repellents mask the mosquitoes’ ability to detect odors. But Odysseus said to the dear nurse Eurycleia: ‘‘Bring sulphur, old dame, to cleanse from pollution, and bring me fire, that I may purge the hall; and do thou bid Penelope come hither with her handmaidens, and order all the women in the house to come.’’ -Homer, Odyssey Chemical repellents for biting pests have long been used by our human ancestors
[1]. The active use of repellents has even been observed in our primate relatives, who crush millipedes and wipe the residue on their fur as a chemical defense against pests like mosquitoes [2,3]. Today, we luckily do not need to use fire and sulfur in our homes, or squash arthropods and wipe them in our hair. Instead, there are many different synthetic repellents available that reduce biting, including DEET, picaridin, and IR 3535 [4]. These repellents have two different modes for preventing bites: some repel
R1124 Current Biology 29, R1122–R1148, November 4, 2019 ª 2019 Elsevier Ltd.
pests at a distance [4,5], whereas others influence the pests once they land on the host [5,6]. In general, the best repellents do both. DEET, or N,N-diethyl-3methylbenzamide, is the ‘gold standard’ of repellents with its long-lasting repellency of diverse arthropod species, including mosquitoes, ticks, fleas and flies [4,7]. The chemical and physical properties of repellents, including DEET, are critical for their efficacy. DEET and its predecessor (N,N-diethylbenzamide) were engineered
Current Biology
Dispatches
D
EE
T
to have low volatility and thus remain at high concentrations on the users’ skin or clothes for extended periods. This is an important feature since highly volatile compounds will quickly evaporate and lose their efficacy over time. In the liquid phase, and once applied to the skin, these synthetic compounds will interact with the volatiles associated with the skin, thus altering and lowering emissions of these volatiles. Despite the efficacy of repellents like DEET, we know little about the molecular basis of how DEET impacts the mosquito’s sensory systems. In the yellow-fever mosquito (Aedes aegypti) and southern house mosquito (Culex quinquefasciatus), stimulation with DEET elicits antennal (electroantennogram) and olfactoryreceptor-neuron responses [5,8]. Mosquito olfactory-receptor neurons express odorant receptors and the odorant coreceptor, orco, which is critical for receptor functioning. In a seminal study, DeGennaro et al. [5] created mutations in orco of the yellow-fever mosquito and showed that orco mutants were insensitive to DEET, whereas wildtype mosquitoes still showed a reduction in attraction. In another important study, ectopic expression of the Cx. quinquefasciatus odorant receptor CquiOr136 in Xenopus oocytes revealed that this receptor was activated by DEET [9] and was responsible for mediating this mosquito’s aversive behavior to DEET [8]. These results, as well as how DEET lowers emission rates of skin volatiles, have given rise to three different hypotheses for how DEET modulates mosquito olfactory responses: DEET may activate a select number of odorant receptors to trigger repellency (so-called ‘smell and repel’ model); DEET may activate and inhibit many odorant receptors at once and therefore act as a ‘confusant’; and lastly, DEET may interfere with the detection of attractive odorants. Nonetheless, it remains unclear if DEET affects all mosquito species in the same manner, and whether all repellents have the same mode of action. Now, in this issue of Current Biology, Afify et al. [10] show that DEET masks attractive odors in the malaria-vector mosquito, Anopheles coluzzii, but only when DEET (or other repellents) are directly mixed with the odorants (like on the skin surface). To explore how
Skin surface
Figure 1. DEET’s suppression of odorant detection in An. coluzzii mosquitoes. In the liquid phase, and once applied to the surface of the skin, the non-volatile nature of certain repellents, like DEET, can reduce the emission of odorants from the skin and associated microbiota, making a person less attractive to foraging mosquitoes. However, research has also suggested that DEET may also operate as an odorant and repel mosquitoes from a distance. Afify et al. [10] demonstrate that for An. coluzzii mosquitoes, DEET suppresses the volatility of odorants, and that these mosquitoes are unable to detect DEET.
repellents modulate the detection of host odors, the authors created a transgenic An. coluzzii line that expresses the fluorescent calcium indicator GCaMP6f in olfactory sensory neurons. This was accomplished using the QF2/QUAS binary system, first developed by Potter and coworkers in Drosophila [11]. Afify and coworkers [10] used a transgenic mosquito that contained the regulatory genomic region for orco in An. coluzzii upstream of the sequence coding for the QF2 transcription factor. This method was first elegantly demonstrated by Riabinina et al. [12]. In tandem, the authors created a QUAS-GCaMP6f reporter line. When the mosquito lines are crossed, the QF2 is expressed, and it binds to the QUAS sequences, leading to expression of GCaMP6f in the orco-expressing neurons. The authors were thus able to functionally image the odor-evoked responses by olfactory receptor neurons on the mosquito olfactory appendages (the antennae, maxillary palps, and labella) and examine how repellents — both synthetic (picaridin, IR 3535, DEET), and natural (lemongrass, eugenol) — modulate those responses.
In contrast to the studies in Cx. quinquefasciatus or Ae. aegypti, Afify et al. [11] found that 100% DEET did not evoke calcium responses in the olfactory receptor neurons. Moreover, other synthetic repellents evoked either no response (IR 3535) or a very weak response (picaridin). However, both common odorants and natural repellents, like lemongrass oil or eugenol, evoked strong olfactory-receptor-neuron responses. How then do DEET and other repellents impact An. coluzzii biting preferences? In a series of carefully controlled experiments, the authors found that DEET masks odorants if they are mixed in the liquid phase. By contrast, if DEET is kept separate from the odorants, but co-released in the air at the same time as the odorants, then the masking effect is lost, and olfactory receptor neurons respond to the odorants similarly to when DEET is absent (Figure 1). Using a photoionization detector — which qualitatively measures the volatiles in the air — the authors were able to verify that the repellents lowered the volatility of odorants, thereby decreasing the concentration reaching the antennae. The
Current Biology 29, R1122–R1148, November 4, 2019 R1125
Current Biology
Dispatches authors were thus able to demonstrate that repellents can have multiple modes of action. On one hand, repellents like lemongrass may activate multiple types of olfactory receptor neurons, leading to a confusant effect in the mosquito, and on the other hand, DEET or any other nonvolatile repellent may suppress the volatile emissions from the skin, making it more difficult for An. coluzzii mosquitoes to detect us (Figure 1). This work has important implications for repellent design, but also raises questions for why some mosquito species detect DEET, but not others. First, there is arguably a need for new repellents that are non-toxic and can alter the skin’s odor to make it functionally non-attractive to mosquitoes. Using non-volatile compounds to suppress the volatility of odorants from the skin microbiota — thereby potentially rendering an individual olfactorily invisible to the mosquito — could be an important avenue to explore for interventions to prevent biting by An. coluzzii, a primary malaria vector in many regions of Africa. Afify et al. [11] also raise the question of how and why DEET differentially affects other mosquito species, or other biting pests. In Ae. aegypti and Cx. quinquefasciatus, research has suggested that DEET activates olfactory receptor neurons to operate as a spatial repellent, and DEET has been hypothesized to mimic natural plant-defensive compounds, like methyl jasmonate [10]. Examining the functional and genetic differences in the olfactory receptors between mosquito species could shed light on how DEET is detected and transduced by olfactory receptor neurons. Moreover, across insects, olfactory receptors are extremely diverse and relate to the ecology and evolutionary history of the insect species. Thus, it’s perhaps not surprising that DEET may function as an odorant for some insects, but not others. Another critical point to recognize is that DEET also acts as a contact repellent, potentially activating the touch or taste receptors located on the mosquito tarsae [6,13]. This contact repellency could explain the broad efficacy of DEET and related repellents across other biting pests, like flies, or even ticks, which lack orco and olfactory receptors. Future work will be needed to examine how repellents like DEET influence other sensory channels in
mosquitoes, like touch, taste, or other chemosensory receptors. Nonetheless, the authors’ development of the QF2/ QUAS binary expression system in mosquitoes provides exciting opportunities to explore these sensory channels, as well as other biological processes that can be leveraged for the control of human-disease vectors. REFERENCES 1. Herodotus. (1996 reprint). The Histories (London: Penguin).
repelled by volatile DEET. Nature 498, 487–491. 6. Dennis, E.J., Goldman, O.V., and Vosshall, L.B. (2019). Aedes aegypti mosquitoes use their legs to sense DEET on contact. Curr. Biol. 29, 1551–1556. 7. DeGennaro, M. (2015). The mysterious multimodal repellency of DEET. Fly 9, 45–51. 8. Syed, Z., and Leal, W.S. (2008). Mosquitoes smell and avoid the insect repellent DEET. Proc. Natl. Acad. Sci. USA 105, 13598–13603. 9. Xu, P., Choo, Y.M., De La Rosa, A., and Leal, W.S. (2014). Mosquito odorant receptor for DEET and methyl jasmonate. Proc. Natl. Acad. Sci. USA 111, 16592–16597.
2. Valderrama, X., Robinson, J.G., Attygalle, A.B., and Eisner, T. (2000). Seasonal anointment with millipedes in a wild primate: a chemical defense against insects? J. Chem. Ecol. 26, 2781–2790.
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Termite Evolution: A Primal Knock on Wood or a Hearty Mouthful of Dirt Michael S. Engel Division of Entomology, Natural History Museum, and Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence, KS 66045, USA Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.09.016
Termite success is inexorably linked to their diet and symbiotic cellulolytic intestinal microorganisms. A new study reveals that soil feeding may have triggered a turnover in intestinal symbionts, rather than ectosymbiont cultivation, allowing termites to achieve ecological dominance. The link between wood consumption and the ecological success of termites is axiomatic. It is a universally acknowledged truth that the appearance
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of termites (infraorder Isoptera) from amongst the roaches (order Blattaria) was made possible by the integration of protistan endosymbionts, thus permitting