scholarly journals Novel small molecule agonists of an Aedes aegypti neuropeptide Y receptor block mosquito biting behavior

2018 ◽  
Author(s):  
Laura B. Duvall ◽  
Lavoisier Ramos-Espiritu ◽  
Kyrollos E. Barsoum ◽  
J. Fraser Glickman ◽  
Leslie B. Vosshall
Keyword(s):  
Aedes Aegypti ◽  
Neuropeptide Y ◽  
Small Molecule ◽  
Blood Meal ◽  
Disease Transmission ◽  
Blood Feeding ◽  
Behavioral Suppression ◽  
Host Seeking ◽  
Novel Approach ◽  
Seeking Behavior

AbstractFemale Aedes aegypti mosquitoes bite humans to obtain a blood-meal to develop their eggs. Remarkably, strong attraction to humans is suppressed for several days after the blood-meal by an unknown mechanism. We investigated a role for neuropeptide Y (NPY)-related signaling in this long-term behavioral suppression, and discovered that drugs targeting human NPY receptors modulate mosquito host-seeking behavior. In a screen of all 49 predicted Ae. aegypti peptide receptors, we identified NPY-like receptor 7 (NPYLR7) as the sole target of these human drugs. To obtain small molecule agonists selective for NPYLR7, we carried out a high-throughput cell-based assay of 265,211 compounds, and isolated 6 highly selective NPYLR7 agonists that inhibit mosquito attraction to humans. NPYLR7 CRISPR-Cas9 null mutants are defective in behavioral suppression, and resistant to these drugs. Finally, we show that these drugs are capable of inhibiting biting and blood-feeding on a live host, suggesting a novel approach to control infectious disease transmission by controlling mosquito behavior.

scholarly journals The oviposition cue indole inhibits animal-host attraction in Aedes aegypti mosquitoes

2021 ◽  
Author(s):  
Amir Dekel ◽  
Evyatar Sar-Shalom ◽  
Esther Yakir ◽  
Jonathan Daniel Bohbot
Keyword(s):  
Aedes Aegypti ◽  
Long Range ◽  
Disease Transmission ◽  
Odorant Receptor ◽  
Host Attraction ◽  
Animal Host ◽  
Insect Repellents ◽  
Host Seeking ◽  
Spatial Repellent ◽  
Seeking Behavior

Abstract Mosquitoes represent a major source of disease transmission and possess the uncanny ability to locate suitable animal-hosts, a feature mediated by their exquisite olfactory system. Insect repellents such as N,N-Diethyl-meta-toluamide, also called DEET, have been shown to activate and inhibit mosquito odorant receptors resulting in behavioral modulation. This and other repellents available for personal protection against mosquitoes are topically applied on the skin and operate at short range. In our search for potential long-range odorant repellents, we have hypothesized that the shared chemical similarities between indole and DEET, may confer the former the ability to block odorant receptor function and inhibit human-host attraction. Using the two-electrode voltage clamp of Xenopus laevis oocytes as a pharmacological platform, we provide evidence that indole inhibits the Aedes aegypti (R)-1-octen-3-ol receptor OR8, a receptor involved in the decision of female mosquitoes to identify human hosts. Coincidentally, we also show that indole inhibits the animal-host seeking behavior of female Aedes aegypti. Together, our findings suggests that indole may be a candidate spatial repellent for the long-range protection of humans against mosquito bites.

scholarly journals The need for practical insecticide-resistance guidelines to effectively inform mosquito-borne disease control programs

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Alice Namias ◽  
Ndey Bassin Jobe ◽  
Krijn Petrus Paaijmans ◽  
Silvie Huijben
Keyword(s):  
Insecticide Resistance ◽  
Disease Control ◽  
Vector Control ◽  
Disease Transmission ◽  
Blood Feeding ◽  
Exposure Dose ◽  
Local Conditions ◽  
Control Programs ◽  
Host Seeking ◽  
Seeking Behavior

Monitoring local mosquito populations for insecticide resistance is critical for effective vector-borne disease control. However, widely used phenotypic assays, which are designed to monitor the emergence and spread of insecticide resistance (technical resistance), do not translate well to the efficacy of vector control products to suppress mosquito numbers in the field (practical resistance). This is because standard testing conditions such as environmental conditions, exposure dose, and type of substrate differ dramatically from those experienced by mosquitoes under field conditions. In addition, field mosquitoes have considerably different physiological characteristics such as age and blood-feeding status. Beyond this, indirect impacts of insecticide resistance and/or exposure on mosquito longevity, pathogen development, host-seeking behavior, and blood-feeding success impact disease transmission. Given the limited number of active ingredients currently available and the observed discordance between resistance and disease transmission, we conclude that additional testing guidelines are needed to determine practical resistance—the efficacy of vector control tools under relevant local conditions— in order to obtain programmatic impact.

scholarly journals Haematophagous arthropod saliva and host defense system: a tale of tear and blood

2005 ◽  
Vol 77 (4) ◽  
pp. 665-693 ◽  
Author(s):  
Bruno B. Andrade ◽  
Clarissa R. Teixeira ◽  
Aldina Barral ◽  
Manoel Barral-Netto
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Host Defense ◽  
Blood Meal ◽  
Disease Transmission ◽  
Blood Feeding ◽  
Defense System ◽  
Current Information ◽  
System A ◽  
Host Defense System

The saliva from blood-feeding arthropod vectors is enriched with molecules that display diverse functions that mediate a successful blood meal. They function not only as weapons against host's haemostatic, inflammatory and immune responses but also as important tools to pathogen establishment. Parasites, virus and bacteria taking advantage of vectors' armament have adapted to facilitate their entry in the host. Today, many salivary molecules have been identified and characterized as new targets to the development of future vaccines. Here we focus on current information on vector's saliva and the molecules responsible to modify host's hemostasis and immune response, also regarding their role in disease transmission.

scholarly journals Effect of Dinotefuran, Permethrin, and Pyriproxyfen (Vectra® 3D) on the Foraging and Blood-Feeding Behaviors of Aedes albopictus Using Laboratory Rodent Model

Insects ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 507
Author(s):  
Younes Laidoudi ◽  
Djamel Tahir ◽  
Hacène Medkour ◽  
Marie Varloud ◽  
Oleg Mediannikov ◽  
...  
Keyword(s):  
Aedes Albopictus ◽  
Selection Index ◽  
Exposure Period ◽  
Blood Feeding ◽  
Feeding Behaviors ◽  
Host Seeking ◽  
Seeking Behavior ◽  
Feeding Effect ◽  
Rats And Mice ◽  
And Control

Dinotefuran-Permethrin-Pyriproxyfen (DPP) is used to kill and repel mosquitoes from dogs. However, the influence of the product on the host-seeking behavior of mosquitoes remains unknown. The interference of DPP with the host selection of unfed female Aedes albopictus was investigated. A total of 18 animals (9 mice and 9 rats) were divided into three groups of six animals each. DU: DPP treated rats (n = 3) with untreated mice (n = 3), UD: DPP treated mice (n = 3) with untreated rats (n = 3) and control UU: untreated mice (n = 3) and untreated rats (n = 3). In each group, the rats and mice were placed 30 cm apart. After sedation, the animals in each group were exposed twice (Day 1 and Day 7 post-treatment) for one hour to 71 ± 3 female mosquitoes. Mosquitoes were categorized after the 2-h post-exposure period as dead or alive. Blood-meal origin was determined from mosquitoes using a newly customized duplex qPCR. The highest values of forage ratio (1.36 ≥ wi ≤ 1.88) and selection index (0.63 ≥ Bi ≤ 0.94) for rat hosts indicates a preference of mosquitoes for this species as compared to mice when co-housed during the exposure. The mosquitoes only seldom fed on mice, even in the untreated group. The anti-feeding effect of DPP was therefore only assessed on rat’s hosts. The results showed that DPP, when directly applied on rats, provided a direct protection of 82% and 61% on Day 1 and Day 7, respectively, while when applied on mice hosts (UD), the DPP provided an indirect protection of 21% and 10% on Day 1 and Day 7, respectively. The results showed also that DPP, when applied on rats, provided a direct protection against Ae. albopictus bites. This effect did not result in increased exposure of the untreated host placed in the same cage at a distance of 30 cm.

scholarly journals Evolutionary transition from blood feeding to obligate nonbiting in a mosquito

2017 ◽  
Vol 115 (5) ◽  
pp. 1009-1014 ◽  
Author(s):  
William E. Bradshaw ◽  
Joshua Burkhart ◽  
John K. Colbourne ◽  
Rudyard Borowczak ◽  
Jacqueline Lopez ◽  
...  
Keyword(s):  
Blood Meal ◽  
Disease Transmission ◽  
Blood Feeding ◽  
Evolutionary Transition ◽  
Genetic Changes ◽  
Wyeomyia Smithii ◽  
Extant Species ◽  
Starting Point ◽  
Differential Gene ◽  
Vector Borne

The spread of blood-borne pathogens by mosquitoes relies on their taking a blood meal; if there is no bite, there is no disease transmission. Although many species of mosquitoes never take a blood meal, identifying genes that distinguish blood feeding from obligate nonbiting is hampered by the fact that these different lifestyles occur in separate, genetically incompatible species. There is, however, one unique extant species with populations that share a common genetic background but blood feed in one region and are obligate nonbiters in the rest of their range: Wyeomyia smithii. Contemporary blood-feeding and obligate nonbiting populations represent end points of divergence between fully interfertile southern and northern populations. This divergence has undoubtedly resulted in genetic changes that are unrelated to blood feeding, and the challenge is to winnow out the unrelated genetic factors to identify those related specifically to the evolutionary transition from blood feeding to obligate nonbiting. Herein, we determine differential gene expression resulting from directional selection on blood feeding within a polymorphic population to isolate genetic differences between blood feeding and obligate nonbiting. We show that the evolution of nonbiting has resulted in a greatly reduced metabolic investment compared with biting populations, a greater reliance on opportunistic metabolic pathways, and greater reliance on visual rather than olfactory sensory input. W. smithii provides a unique starting point to determine if there are universal nonbiting genes in mosquitoes that could be manipulated as a means to control vector-borne disease.

scholarly journals On the use of inhibitors of 4-hydroxyphenylpyruvate dioxygenase as a vector-selective insecticide in the control of mosquitoes

2019 ◽  
Author(s):  
Marlon A. V. Ramirez ◽  
Marcos Sterkel ◽  
Ademir de Jesus Martins ◽  
José Bento Pereira Lima ◽  
Pedro L. Oliveira
Keyword(s):  
Amino Acids ◽  
Body Weight ◽  
Aedes Aegypti ◽  
Blood Meal ◽  
Mosquito Control ◽  
Blood Feeding ◽  
Degradation Pathway ◽  
Cross Resistance ◽  
Single Meal ◽  
Neurotoxic Insecticides

AbstractBlood-sucking insects incorporate many times their body weight of blood in a single meal. As proteins are the major component of vertebrate blood, its digestion in the gut of hematophagous insects generates extremely high concentrations of free amino acids. Previous reports showed that the tyrosine degradation pathway plays an essential role in adapting these animals to blood feeding. Inhibiting 4-hydroxyphenylpyruvate dioxygenase (HPPD), the rate-limiting step of tyrosine degradation, results in the death of insects after a blood meal. Therefore, it was suggested that compounds that block the catabolism of tyrosine could act selectively on blood-feeding insects. Here we have evaluated the toxicity against mosquitoes of three HPPD inhibitors currently used as herbicides and in human health. Among the compounds tested, nitisinone (NTBC) proved to be more potent than mesotrione (MES) and isoxaflutole (IFT) in Aedes aegypti. NTBC was lethal to Ae. aegypti in artificial feeding assays (LD50: 4.36 µM), as well as in topical application (LD50: 0.0033 nmol/mosquito). NTBC was also lethal to Ae. aegypti populations that were resistant to neurotoxic insecticides, and it was lethal to other mosquito species (Anopheles and Culex). Therefore, HPPD inhibitors, particularly NTBC, represent promising new drugs for mosquito control. Since they only affect blood-feeding organisms, they would represent a safer and more environmentally friendly alternative to conventional neurotoxic insecticides.Author SummaryThe control of mosquitoes has been pursued in the last decades by the use of neurotoxic insecticides to prevent the spreading of dengue, zika and malaria, among other diseases. However, the selection and propagation of different mechanisms of resistance hinder the success of these compounds. New methodologies are needed for their control. Hematophagous arthropods, including mosquitoes, ingest quantities of blood that represent many times their body weight in a single meal, releasing huge amounts of amino acids during digestion. Recent studies showed that inhibition of the tyrosine catabolism pathway could be a new selective target for vector control. Thus we tested three different inhibitors of the second enzyme in the tyrosine degradation pathway as tools for mosquito control. Results showed that Nitisinone (NTBC), an inhibitor used in medicine, was the most potent of them. NTBC was lethal to Aedes aegypti when it was administered together with the blood meal and when it was topically applied. It also caused the death of Anopheles aquasalis and Culex quinquefasciatus mosquitoes, as well as field-collected Aedes populations resistant to neurotoxic insecticides, indicating that there is no cross-resistance. We discuss the possible use of NTBC as a new insecticide.

scholarly journals Assessing the blood-host plasticity and dispersal rate of the malaria vector Anopheles coluzzii

2018 ◽  
Author(s):  
James Orsborne ◽  
Luis Furuya-Kanamori ◽  
Claire L. Jeffries ◽  
Mojca Kristan ◽  
Abdul Rahim Mohammed ◽  
...  
Keyword(s):  
Blood Meal ◽  
Disease Transmission ◽  
Blood Feeding ◽  
Host Choice ◽  
Anopheles Coluzzii ◽  
Dispersal Rate ◽  
Blood Digestion ◽  
Novel Method ◽  
Blood Meal Digestion ◽  
Blood Meals

AbstractDifficulties with observing the dispersal of insect vectors in the field have hampered understanding of several aspects of their behaviour linked to disease transmission. Here, a novel method based on detection of blood-meal sources is introduced to inform two critical and understudied mosquito behaviours: plasticity in the malaria vector’s blood-host choice and vector dispersal. Strategically located collections of Anopheles coluzzii from a malaria-endemic village of southern Ghana showed statistically significant variation in host species composition of mosquito blood-meals. Trialling a new sampling approach gave the first estimates for the remarkably local spatial scale across which host choice is plastic. Using quantitative PCR, the blood-meal digestion was then quantified for field-caught mosquitoes and calibrated according to timed blood digestion in colony mosquitoes. We demonstrate how this new ‘molecular Sella score’ approach can be used to estimate the dispersal rate of blood-feeding vectors caught in the field.

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