Mosquito Olfaction Research Articles

Mosquito Embryo Microinjection.

Genetically modified (GM) mosquitoes are an important tool in the fight against mosquito-borne disease, both indirectly through their use in research investigating host-pathogen interaction, mosquito olfaction, and anthropomorphic behavior and in future direct uses for suppression and possibly eradication through sterile insect technique (SIT) and/or gene-drive programs. Successful creation of GM mosquitoes depends on microinjection procedures that precisely deliver injection materials while causing as little damage to mosquito embryos as possible. Genetic modification reagents, such as transposon system components (vector plasmids, helper plasmids, and helper mRNA), and CRISPR-Cas9 components (guide RNAs, Cas9 protein, plasmids expressing Cas9 and/or guide RNAs, and donor plasmids used in homology-directed repair [HDR]), must be delivered into the preblastoderm embryo at the posterior end where the pole cells will form before cellularization occurs. Sharp needles that pierce the embryo easily are important tools in this procedure and work best when the embryos are not desiccated. The two main procedures for mosquito embryo microinjection involve injecting embryos under halocarbon oil or under aqueous solution.

Effect of Temperature on Mosquito Olfaction.

Mosquitoes use a wide range of cues to find a host to feed on, eventually leading to the transmission of pathogens. Among them, olfactory cues (e.g., host-emitted odors, including CO2, and skin volatiles) play a central role in mediating host-seeking behaviors. While mosquito olfaction can be impacted by many factors, such as the physiological state of the insect (e.g., age, reproductive state), the impact of environmental temperature on the olfactory system remains unknown. In this study, we quantified the behavioral responses of Aedes aegypti mosquitoes, vectors of dengue, yellow fever, and Zika viruses, among other pathogens, to host and plant-related odors under different environmental temperatures.

Genetically Encoded Calcium Indicators for Functional Imaging of Mosquito Olfactory Neurons.

Mosquitoes transmit a multitude of diseases to humans and animals through biting and blood feeding. To locate their hosts, mosquitoes primarily use their sense of smell. Therefore, an understanding of mosquito olfaction will help develop strategies to control the diseases they transmit. A mosquito's sense of smell is determined by the response of olfactory neurons on its peripheral olfactory organs. Traditionally, mosquito olfactory neuron activity has been examined using electrophysiological techniques such as electroantennography and single sensillum recordings. Electroantennography examines if an odorant is detectable by the ensemble of all antennal neurons. In contrast, single sensillum electrophysiology allows detailed recordings of the activity of two to three neurons at a time. However, single sensillum recording of olfactory neurons is difficult, laborious, and typically allows examination of only a few neurons on the antenna. A promising new approach is to use optical imaging techniques to provide a way to visualize the global response of olfactory organs to an odor, as well as the specific responses of several olfactory neurons to that odor. In particular, calcium imaging has progressed significantly, from the use of chemical calcium indicators to the development of genetically encoded calcium sensors. These advances have opened the way to study the mode of action of known mosquito attractants and repellents as well as a way to screen potential new attractants and repellents. Here, we provide an introduction to the different types of calcium indicators and their uses for investigating the function of mosquito sensory neurons.

Mosquito Electroantennography.

Mosquitoes use multiple cues to locate food sources (animal and plants), mates, and oviposition sites. The sense of smell plays an important role in these behaviors, and olfactory cues are detected primarily by the appendages on the head-in particular, the antennae. Thus, mosquito olfaction can be studied by conducting electroantennogram (EAG) recordings. EAGs have emerged as a reliable technique to screen for bioactive compounds and are useful in the development of attractants and repellents for mosquito population control. Here, we focus on comparing the two main experimental approaches used in the literature (whole-body and whole-head mounting) and highlight key considerations for conducting EAGs in multiple species and for obtaining reliable and reproducible data.

A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness

The host-seeking activity of hematophagous arthropods is essential for arboviral transmission. Here, we demonstrate that mosquito-transmitted flaviviruses can manipulate host skin microbiota to produce a scent that attracts mosquitoes. We observed that Aedes mosquitoes preferred to seek and feed on mice infected by dengue and Zika viruses. Acetophenone, a volatile compound that is predominantly produced by the skin microbiota, was enriched in the volatiles from the infected hosts to potently stimulate mosquito olfaction for attractiveness. Of note, acetophenone emission was higher in dengue patients than in healthy people. Mechanistically, flaviviruses infection suppressed the expression of RELMα, an essential antimicrobial protein on host skin, thereby leading to the expansion of acetophenone-producing commensal bacteria and, consequently, a high acetophenone level. Given that RELMα can be specifically induced by a vitamin A derivative, the dietary administration of isotretinoin to flavivirus-infected animals interrupted flavivirus life cycle by reducing mosquito host-seeking activity, thus providing a strategy of arboviral control.

Biting Innovations of Mosquito-Based Biomaterials and Medical Devices.

Mosquitoes are commonly viewed as pests and deadly predators by humans. Despite this perception, investigations of their survival-based behaviors, select anatomical features, and biological composition have led to the creation of several beneficial technologies for medical applications. In this review, we briefly explore these mosquito-based innovations by discussing how unique characteristics and behaviors of mosquitoes drive the development of select biomaterials and medical devices. Mosquito-inspired microneedles have been fabricated from a variety of materials, including biocompatible metals and polymers, to mimic of the mouthparts that some mosquitoes use to bite a host with minimal injury during blood collection. The salivary components that these mosquitoes use to reduce the clotting of blood extracted during the biting process provide a rich source of anticoagulants that could potentially be integrated into blood-contacting biomaterials or administered in therapeutics to reduce the risk of thrombosis. Mosquito movement, vision, and olfaction are other behaviors that also have the potential for inspiring the development of medically relevant technologies. For instance, viscoelastic proteins that facilitate mosquito movement are being investigated for use in tissue engineering and drug delivery applications. Even the non-wetting nanostructure of a mosquito eye has inspired the creation of a robust superhydrophobic surface coating that shows promise for biomaterial and drug delivery applications. Additionally, biosensors incorporating mosquito olfactory receptors have been built to detect disease-specific volatile organic compounds. Advanced technologies derived from mosquitoes, and insects in general, form a research area that is ripe for exploration and can uncover potential in further dissecting mosquito features for the continued development of novel medical innovations.

Odorant inhibition in mosquito olfaction mediated by inverse agonists

The insect repellent methyl salicylate elicits excitatory responses upon interaction with CquiOR32, an odorant receptor (OR) from the southern house mosquito, Culex quinquefasciatus. By contrast, eucalyptol binds to CquiOR32 to generate electrophysiological and behavioral inhibitory responses. In an attempt to identify CquiOR32 variants displaying more robust inhibitory responses for more accurate current-voltage analysis, we sequenced 31 CquiOR32 clones. In the Xenopus oocyte recording system, CquiOR32V2/CquiOrco-expressing oocytes yielded eucalyptol-elicited outward (inhibitory) currents relatively larger than methyl salicylate-generated inward (excitatory) currents. Rescuing experiments showed that two of the amino acid substitutions in CquiOR32V2 located in a predicted transmembrane helix of the receptor are determinants of the outward/inward ratios. These findings, along with co-stimulus assays, suggest that odorant and inhibitor may bind to the same binding pocket. Current-voltage relationships obtained with standard perfusion buffer and those devoid of Na+ or Cl− indicated that both excitatory and inhibitory currents are mediated, at least in part, by cation. We then concluded that eucalyptol is an inverse agonist, which shifts the open ⇔ closed equilibrium of the receptor toward the closed conformation, thus reducing the spontaneous activity. By contrast, the binding of methyl salicylate shifts the equilibrium towards the open conformation and, consequently, leads to an increase in cation influx.

Olfaction in Anopheles mosquitoes.

As vectors of disease, mosquitoes are a global threat to human health. The Anopheles mosquito is the deadliest mosquito species as the insect vector of the malaria-causing parasite, which kills hundreds of thousands every year. These mosquitoes are reliant on their sense of smell (olfaction) to guide most of their behaviors, and a better understanding of Anopheles olfaction identifies opportunities for reducing the spread of malaria. This review takes a detailed look at Anopheles olfaction. We explore a range of topics from chemosensory receptors, olfactory neurons, and sensory appendages to behaviors guided by olfaction (including host-seeking, foraging, oviposition, and mating), to vector management strategies that target mosquito olfaction. We identify many research areas that remain to be addressed.

The mosquito taste system and disease control

Mosquitoes are a widely diverse group of organisms, comprising ∼3,500 species that live in an enormous range of habitats. Some species are vectors of diseases that afflict hundreds of millions of people each year. Although understanding of mosquito olfaction has progressed dramatically in recent years, mosquito taste remains greatly understudied. Since taste is essential to feeding, egg laying, and mating decisions in insects, improved understanding of taste in mosquitoes could provide new mechanistic insight into many aspects of their behavior. We provide a guide to current knowledge in the field, and we suggest a wealth of opportunities for research that are now enabled by recent scientific and technological advances. We also propose means by which taste might be exploited in new strategies for mosquito control, which may be urgently needed as the geographical ranges of vector species increase with climate change.

Neuronal Odor Coding in the Larval Sensory Cone of <i>Anopheles Coluzzii</i>: Complex Responses from a Simple System

Anopheles mosquitoes are the sole vectors of malaria and other diseases that represent significant threats to global public health. While adult female mosquitoes are responsible for disease transmission, the pre-adult larval stages of the malaria vector Anopheles coluzzii and other mosquitoes rely on a broad spectrum of sensory cues to navigate their aquatic habitats efficiently to avoid predators and search for food. Of these, mosquito larvae rely heavily on volatile chemical signals that directly activate their olfactory apparatus. Because most studies on mosquito olfaction focus on adults, a paucity of attention has been given to the larval olfactory system, in which the peripheral components are associated with the sensory cone of the larval antennae. To address this, we have investigated the electrophysiological response profile of the larval sensory cone in Anopheles mosquitoes. We found that the larval sensory cone is particularly tuned to alcohols, thiazoles and heterocyclics. Furthermore, these responses can be assigned to discrete groups of sensory cone neurons with distinctive, dose-dependent odorant-response profiles that also provide larvae with the ability to discriminate among compounds with similar chemical structures. A correlation analysis was conducted to determine the relationship between specific larval chemosensory receptors and the response profiles of sensory cone neuron groups. These studies reveal that the larval sensory cone is a highly sophisticated organ that is sensitive to a broad range of compounds and is capable of a remarkable degree of chemical discrimination. Taken together, this study presents critical insights into olfactory coding processes in An. coluzzii larvae that further our understanding of larval chemical ecology and will contribute to the development of novel larval-based strategies and tools for mosquito control and the reduction of vector-borne disease transmission.

Odorant Inhibition in Mosquito Olfaction.

SummaryHow chemical signals are integrated at the peripheral sensory system of insects is still an enigma. Here we show that when coexpressed with Orco in Xenopus oocytes, an odorant receptor from the southern house mosquito, CquiOR32, generated inward (regular) currents when challenged with cyclohexanone and methyl salicylate, whereas eucalyptol and fenchone elicited inhibitory (upward) currents. Responses of CquiOR32-CquiOrco-expressing oocytes to odorants were reduced in a dose-dependent fashion by coapplication of inhibitors. This intrareceptor inhibition was also manifested in vivo in fruit flies expressing the mosquito receptor CquiOR32, as well in neurons on the antennae of the southern house mosquito. Likewise, an orthologue from the yellow fever mosquito, AaegOR71, showed intrareceptor inhibition in the Xenopus oocyte recording system and corresponding inhibition in antennal neurons. Inhibition was also manifested in mosquito behavior. Blood-seeking females were repelled by methyl salicylate, but repellence was significantly reduced when methyl salicylate was coapplied with eucalyptol.

Variant Ionotropic Receptors are Expressed in the Antennae of Anopheles sinensis (Diptera: Culicidae).

Mosquitoes transmit many harmful diseases that seriously threaten public health. The mosquito's olfactory system is of great significance for host selection. Inotropic receptors (IRs) and olfactory receptors (ORs) have been demonstrated to be capable of odorant molecular recognition. Analyzing the molecular principles of mosquito olfaction facilitates the development of prevention and therapy techniques. Advances in the understanding of IRs have been seriously inadequate compared to those of ORs. Here, we provide evidence that 35 Anopheles sinensis IR (AsIR) genes are expressed, 7 of which are in the antennae and 2 have expression levels that are upregulated with a blood meal. A homologous analysis of the sequences showed that AsIRs are a subfamily of ionotropic glutamate receptors (iGLURs). This is the first that time IRs have been identified in Anopheles sinensis in vitro. The ultrastructure of the antennae supports the theory that diverse sensilla are distributed in the antennae. The results here may facilitate the revelation of the regulation mechanism in AsIRs, which could mitigate the transmission of diseases by mosquitoes.

A Synergistic Transcriptional Regulation of Olfactory Genes Drives Blood-Feeding Associated Complex Behavioral Responses in the Mosquito Anopheles culicifacies.

Decoding the molecular basis of host seeking and blood feeding behavioral evolution/adaptation in the adult female mosquitoes may provide an opportunity to design new molecular strategy to disrupt human-mosquito interactions. Although there is a great progress in the field of mosquito olfaction and chemo-detection, little is known about the sex-specific evolution of the specialized olfactory system of adult female mosquitoes that enables them to drive and manage the complex blood-feeding associated behavioral responses. A comprehensive RNA-Seq analysis of prior and post blood meal olfactory system of An. culicifacies mosquito revealed a minor but unique change in the nature and regulation of key olfactory genes that may play a pivotal role in managing diverse behavioral responses. Based on age-dependent transcriptional profiling, we further demonstrated that adult female mosquito's chemosensory system gradually learned and matured to drive the host-seeking and blood feeding behavior at the age of 5–6 days. A time scale expression analysis of Odorant Binding Proteins (OBPs) unravels unique association with a late evening to midnight peak biting time. Blood meal-induced switching of unique sets of OBP genes and Odorant Receptors (Ors) expression coincides with the change in the innate physiological status of the mosquitoes. Blood meal follows up experiments further provide enough evidence that how a synergistic and concurrent action of OBPs-Ors may drive “prior and post blood meal” associated complex behavioral events. A dominant expression of two sensory appendages proteins (SAP-1 & SAP2) in the legs of An. culicifacies suggests that this mosquito species may draw an extra advantage of having more sensitive appendages than An. stephensi, an urban malarial vector in the Indian subcontinents. Finally, our molecular modeling analysis predicts crucial amino acid residues for future functional characterization of the sensory appendages proteins which may play a central role in regulating multiple behaviors of An. culicifacies mosquito.SIGNIFICANCE Evolution and adaptation of blood feeding behavior not only favored the reproductive success of adult female mosquitoes but also make them important disease-transmitting vectors. An environmental exposure after emergence may favor the broadly tuned olfactory system of mosquitoes to drive complex behavioral responses. But, how these olfactory derived genetic factors manage female specific “pre and post” blood meal associated complex behavioral responses are not well known. Our findings suggest that a synergistic action of olfactory factors may govern an innate to prime learning strategy to facilitate rapid blood meal acquisition and downstream behavioral activities. A species-specific transcriptional profiling and an in-silico analysis predict that “sensory appendages protein” may be a unique target to design disorientation strategy against the mosquito Anopheles culicifacies.

Antennal-expressed ammonium transporters in the malaria vector mosquito Anopheles gambiae.

The principal Afrotropical malaria vector mosquito, Anopheles gambiae remains a significant threat to human health. In this anthropophagic species, females detect and respond to a range of human-derived volatile kairomones such as ammonia, lactic acid, and other carboxylic acids in their quest for blood meals. While the molecular underpinnings of mosquito olfaction and host seeking are becoming better understood, many questions remain unanswered. In this study, we have identified and characterized two candidate ammonium transporter genes, AgAmt and AgRh50 that are expressed in the mosquito antenna and may contribute to physiological and behavioral responses to ammonia, which is an important host kairomone for vector mosquitoes. AgAmt transcripts are highly enhanced in female antennae while a splice variant of AgRh50 appears to be antennal-specific. Functional expression of AgAmt in Xenopus laevis oocytes facilitates inward currents in response to both ammonium and methylammonium, while AgRh50 is able to partially complement a yeast ammonium transporter mutant strain, validating their conserved roles as ammonium transporters. We present evidence to suggest that both AgAmt and AgRh50 are in vivo ammonium transporters that are important for ammonia sensitivity in An. gambiae antennae, either by clearing ammonia from the sensillar lymph or by facilitating sensory neuron responses to environmental exposure. Accordingly, AgAmt and AgRh50 represent new and potentially important targets for the development of novel vector control strategies.

Protein science “best paper” awards to Mark Landau and Brian Ziemba

Warmest congratulations to Brian Ziemba (right) and Mark Landau (left), the recipients of the Protein Society's “Best Paper” awards. At the beginning of each year, two “best papers” are selected from articles published in Protein Science during the preceding 12 months. A junior author (typically the first author) is designated as the award winner and invited to give a talk at the following Annual Protein Society Symposium. Mark Landau received his Bachelor of Science degree in Chemical Biology from UC-Berkeley and Ph.D. in Yale's Department of Molecular Biophysics and Biochemistry. As a graduate student, and now as a postdoctoral associate, his research in the laboratory of Professor Karen Anderson has focused on the mechanisms of enzymes relevant to disease therapy, including HIV-1 reverse transcriptase, the human cytidine deaminase APOBEC3G, and the bifunctional enzyme thymidylate synthase-dihydrofolate reductase (TS-DHFR) from the parasite Toxoplasma gondii. In the future, he hopes to pursue a career in academic research and study the function of enzymes with clinical relevance. Mark's award-winning article1 was the result of probing the TS-DHFR structure and function to aid the design of allosteric inhibitors with increased selectivity. This led to the discovery of peptide inhibitors, which mimic β-strands at the enzyme's dimer interface, that bind specifically to the apo-enzyme form of the parasitic TS-DHFR and inhibit both TS and DHFR activity but do not affect human TS or DHFR. Fluorescence spectroscopy revealed that these peptides take advantage of the enzyme's unique molecular motions to bind and trap it in an inactive conformation. Dr. Anderson commented that “The aspect of Mark's project described in the article was taken up completely as his own initiative. I was supportive but skeptical that it would work. Thankfully, as is often the case, as PIs, we are wrong and the design worked beautifully.” Brian Ziemba's undergraduate studies (University of Colorado, Boulder) focused on molecular biology and biochemistry with the intention of going into medicine. Along the way, he became involved in several undergraduate independent research projects and his interests became more aligned with scientific research. After studying clinical laboratory science (OHSU, Portland, OR), and working nights for 3 years as a medical technologist in Reno, NV, and then in Lafayette, CO, he realized that he belonged in a more research-oriented environment. As a graduate student at the University of Colorado Denver (Anschutz Medical Campus), he joined the lab of Professor David N.M. Jones, where he became interested in structural biology. His main thesis project involved using NMR, X-ray crystallography, and fluorescence methods to explore ethanol:protein interactions in ethanol-sensitive proteins, such as protein kinase Cδ and the GABAρ receptor. Although half of the lab focused on alcohol sensitivity, the other half worked toward the goal of understanding the molecular events of olfactory signaling that guides feeding behavior of the mosquito Anopheles gambiae, the primary vector of the most dangerous form of malaria. This required studies on multiple odorant binding proteins (OBPs), which function to complex with human odorants in order to inform host-seeking behavior, and thus malaria transmission. Because of his prior experience, Brian could help in cloning OBP20 and then went on to pursue crystallographic studies. Interestingly, OBP20 crystals formed differently in response to varying crystallization conditions, yielding insights into the mechanism of odorant ligand binding and release, which occurs in mosquito olfaction and host-seeking processes.2 Resolution of the two states of OBP20 that exist in the process of mosquito olfaction may ultimately be important for knowing which state to target in order to inhibit activity. Prof. Jones comments that “Brian is the perfect example of a great lab member. He takes on jobs completely unknown to me, to help out another lab member. He has continued to provide input and ideas even after leaving the lab.” Brian is currently a postdoc in the lab of Joseph Falke. He says that his future plans are undetermined at this point. As he puts it “Industry appeals to me as a profession where I could potentially contribute to amelioration or detection of human disease while academia continues to draw me to a setting where scientific curiosities and interests are more easily pursued.”

Expression Analysis and Knockdown of Two Antennal Odorant-Binding Protein Genes inAedes aegypti

The presence and expression of odorant-binding proteins (OBPs) in the olfactory organs suggest that they play an important role in mosquito olfaction. However, no direct evidence has been found for their involvement in the host-seeking behavior of mosquitoes. It is important to establish a method in which a loss-of-function test can be performed to determine the possible role of these genes in olfaction. In this study, a double subgenomic Sindbis virus expression system was used to reduce the expression of two Obp genes in Aedes aegypti L (Diptera: Culicidae), AaegObp1 and AaegObp2. Quantitative real-time PCR analysis showed predominant expression of both genes in the female antennae, the primary olfactory tissue of mosquitoes. Moreover, at 11 days post virus-inoculation, the mRNA levels of AaegObp1 and AaegObp2 were significantly reduced in olfactory tissues of recombinant virus-inoculated female mosquitoes compared to that of controls by approximately 8 and 100-fold, respectively. These data suggest that the double subgenomic Sindbis virus expression system can be efficiently used to knockdown Obp gene expression in olfactory tissues of mosquitoes. We discuss the potential for a systematic analysis of the molecular players involved in mosquito olfaction using this newly developed technique. Such analysis will provide an important step to interfere with the host-seeking behavior of mosquitoes to prevent the transmission of diseases.

Mosquito repellents: a review of chemical structure diversity and olfaction

Research on mosquito chemical repellents continues to advance, along with knowledge of mosquito olfaction and behavior, mosquito-host interactions and chemical structure. New tools and technologies have revealed information about insect olfactory mechanisms and processing, providing a more complex approach for the interpretation of how chemical repellents influence host-seeking and feeding behavior. Even with these advances, there is still a large amount of information contained in the early works on insect repellents. Many of the standard test methods and chemicals that are still used for evaluating active repellents were developed in the 1940s. These studies contain valuable references to the activity of different structural classes of chemicals, and serve as a guide to optimization of select compounds for insect repellency effects.

Characterization and expression of the odorant‐binding protein 7 gene in Anopheles stephensi and comparative analysis among five mosquito species

Odorant-binding proteins (OBPs) are important molecular players in insect olfaction, which has a great influence on the host-seeking behaviour of mosquitoes and other disease vectors. The mRNA level of the Anopheles gambiae Obp7 gene (Agam-Obp7) is higher in the adult female antennae and is slightly reduced in the female heads after blood-feeding. Here we report the cloning, sequencing, chromosomal mapping and transcript analysis of Aste-Obp7, the Obp7 gene from the Asian malaria mosquito Anopheles stephensi. Quantitative reverse transcription PCR showed that in adult female mosquitoes, Aste-Obp7 was expressed abundantly in the antennae, much less in pooled maxillary palp and proboscis and at the lowest level in the legs. The Aste-Obp7 level in female antennae was significantly higher than in male antennae and it slightly increased 24 h after a bloodmeal. The same pattern held for leg samples as well. The Aste-Obp7 mRNA level dropped more than 10-fold in the female maxillary palp and proboscis after a bloodmeal, although it was still significantly higher than in the males. Together, the above expression profiles suggest that Aste-Obp7 probably functions in female olfaction and may possibly be involved in behaviour related to blood-feeding. We also characterized the Obp7 gene from Anopheles quadriannulatus. Comparison among Anopheles Obp7 genes revealed conserved noncoding sequences that contain potential regulatory elements. The coding sequence and gene structure of Obp7 as well as local synteny of surrounding genes are conserved among the three Anopheles species and two divergent mosquitoes, Aedes aegypti and Culex pipiens quinquefasciatus. OBP7 protein phylogeny is congruent with the mosquito phylogeny and there is evidence of purifying selection acting on the mosquito Obp7 gene. Comparative genomics analysis will improve our understanding of the evolution and regulation of genes involved in mosquito olfaction.

The role of mosquito olfaction in oviposition site location and in the avoidance of unsuitable hosts.

Developments in the exploitation of mosquito olfaction are traced, in collaborative studies with various groups, from the first identification of a mosquito pheromone through to a discussion of non-host avoidance. The characterization of the oviposition pheromone for mosquitoes in the genus Culex, e.g. Culex quinquefasciatus, as a novel chiral lactone ester provided the impetus for a number of sophisticated asymmetric syntheses and economical large-scale routes to racemic products. The latter have provided material for successful field trials in three continents. During the course of this field work, we obtained evidence that semiochemicals originating directly from the oviposition site are essential for activity of the oviposition pheromone. Recent studies are elucidating the nature of these agents and their geographical variability. Initially, we used synthetic oviposition pheromone to attract mosquitoes to sites treated with a biorational larvicide. However, recyclable biological control agents offer better prospects for resource-poor regions. A biotechnological approach to pheromone production has been devised involving the generation of inexpensive starting materials by the cultivation of a higher plant. New studies on dipterous pests feeding on farm animals indicate a semiochemically based mechanism by which unsuitable individuals within the host species are avoided. There appears to be an analogous process in which mosquitoes avoid certain potential human hosts, thereby raising prospects for the development of novel, rationally identified repellents once the semiochemical/olfactory interactions have been fully elucidated.

Outsmarting Olfaction: The Next Generation of Mosquito Repellents

The world’s most dangerous animal weighs about two milligrams and pursues its human prey at speeds of barely a mile per hour. Surprised? Don’t be. The dubious honor belongs to the lowly mosquito—a fragile creature whose bite infects millions with lethal diseases, such as malaria, dengue, and West Nile encephalitis. For centuries, humans have slathered on insect repellents to deter the buzzing menace—the first recorded repellents were documented by Herodotus around 400 B.C. But these products have always been far from optimal. Even DEET (N,N′-diethyl-n-toluamide), the world’s most popular and efficacious repellent, has numerous shortcomings: it can require frequent applications, it must be applied to all exposed body parts, and it won’t protect against some dangerous mosquito species, including Anopheles albimanus, the chief malaria vector in Central America. Today, the need for more effective repellents is increasingly urgent, experts say. According to the World Health Organization, global climate change is expanding mosquitoes’ range, heightening the risk of disease for millions of additional people. The Centers for Disease Control and Prevention notes that dengue and West Nile virus are both moving from developing countries towards the United States, where concerns over mosquito exposure are rising. Malaria—which by various estimates kills between 1 million and 3 million people worldwide each year—is also a growing problem in many regions. This is in part because Plasmodium, the mosquito-borne parasite that causes malaria, is fast becoming resistant to existing treatments, such as chloroquine. Many experts believe that better repellents could help to control mosquito-borne diseases. These next-generation repellents must be effective against anopheline mosquitoes that carry malaria. They should also be cheap and nontoxic, and should last long enough to protect humans as they sleep, when they are most vulnerable. Where will these repellents come from? The answers, scientists increasingly say, will be found in genomic research. According to this view, knowledge of the genes and proteins that mosquitoes rely on to sense their environment could lead to new repellents that directly interfere with the insects’ ability to detect human beings.