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 Screening for Odorant Receptor Genes Expressed in Aedes Aegypti Involved in Blood-Feeding and Oviposition Behaviors

2021 ◽  
Author(s):  
Meng Ni ◽  
Teng Zhao ◽  
Hui-xin Lv ◽  
Man-jin Li ◽  
Dan Xing ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Olfactory System ◽  
Mosquito Control ◽  
Odorant Receptor ◽  
Blood Feeding ◽  
Differentially Expressed ◽  
Expression Levels ◽  
Blood Sucking ◽  
Or Genes ◽  
Reproductive Processes

Abstract Background: Aedes aegypti is one of the most important vector worldwide, and its survival and reproductive processes depend heavily on the olfactory system. In this study, the expression levels of all odorant receptor (OR) genes of Ae. aegypti were explored in different physiological periods to identify olfactory genes that may be associated with mosquito blood sucking and searching for oviposition sites.Methods: Four groups, consisting of Ae. aegypti males (M), pre-blood-feeding females (F), post-blood-feeding females (B) and post-oviposition females (O), were established. A total of 114 pairs of primer targeting all OR genes were designed based on the whole genome of Ae. aegypti. The expression of OR genes was evaluated by real-time fluorescence quantitative PCR for relative quantification and the comparison of differences between groups.Results: A total of 53 differentially expressed OR genes were identified between males and females in Ae. aegypti antennae. And 8, 5 and 13 differentially expressed OR genes were identified before versus after blood feeding, before versus after oviposition and post-blood-feeding versus post-oviposition, respectively. Meanwhile, 16 OR genes were significantly differentially expressed in multiple physiological periods of mosquitoes.Conclusions: A large number of ORs with significant intergroup differences and high expression levels were screened in this study, including OR75, OR88, OR110 and OR115 and so on. Some of these genes are reported for the first time, providing possible targets for the development of mosquito control pathways based on the olfactory system.

scholarly journals Hormone-dependent activation and repression of microRNAs by the ecdysone receptor in the dengue vector mosquito Aedes aegypti

2021 ◽  
Vol 118 (26) ◽  
pp. e2102417118
Author(s):  
Ya-Zhou He ◽  
Emre Aksoy ◽  
Yike Ding ◽  
Alexander S. Raikhel
Keyword(s):  
Aedes Aegypti ◽  
Mirna Expression ◽  
Blood Meal ◽  
Fat Body ◽  
Blood Feeding ◽  
Small Rna Sequencing ◽  
Sequencing Analysis ◽  
Ecdysone Receptor ◽  
Egg Development ◽  
Semialdehyde Dehydrogenase

Female mosquitoes transmit numerous devastating human diseases because they require vertebrate blood meal for egg development. MicroRNAs (miRNAs) play critical roles across multiple reproductive processes in female Aedes aegypti mosquitoes. However, how miRNAs are controlled to coordinate their activity with the demands of mosquito reproduction remains largely unknown. We report that the ecdysone receptor (EcR)–mediated 20-hydroxyecdysone (20E) signaling regulates miRNA expression in female mosquitoes. EcR RNA-interference silencing linked to small RNA-sequencing analysis reveals that EcR not only activates but also represses miRNA expression in the female mosquito fat body, a functional analog of the vertebrate liver. EcR directly represses the expression of clustered miR-275 and miR-305 before blood feeding when the 20E titer is low, whereas it activates their expression in response to the increased 20E titer after a blood meal. Furthermore, we find that SMRTER, an insect analog of the vertebrate nuclear receptor corepressors SMRT and N-CoR, interacts with EcR in a 20E-sensitive manner and is required for EcR-mediated repression of miRNA expression in Ae. aegypti mosquitoes. In addition, we demonstrate that miR-275 and miR-305 directly target glutamate semialdehyde dehydrogenase and AAEL009899, respectively, to facilitate egg development. This study reveals a mechanism for how miRNAs are controlled by the 20E signaling pathway to coordinate their activity with the demands of mosquito reproduction.

scholarly journals The juvenile hormone receptor Methoprene-tolerant is involved in the sterilizing effect of pyriproxyfen on adult Aedes aegypti mosquitoes

2020 ◽  
Author(s):  
Tahmina Hossain Ahmed ◽  
T. Randolph Saunders ◽  
Donald Mullins ◽  
Mohammad Zillur Rahman ◽  
Jinsong Zhu
Keyword(s):  
Aedes Aegypti ◽  
Juvenile Hormone ◽  
Mosquito Control ◽  
Fat Body ◽  
Control Strategies ◽  
Follicular Development ◽  
Blood Feeding ◽  
Oocyte Development ◽  
Hormonal Responses ◽  
Before And After

AbstractExposure of adult mosquitoes to pyriproxyfen (PPF), an analog of insect juvenile hormone (JH), has shown promise to effectively sterilize female mosquitoes. However, the underlying mechanisms of the PPF-induced decrease in mosquito fecundity are largely unknown. We performed a comprehensive study to dissect the mode of PPF action in Aedes aegypti mosquitoes. Exposure to PPF prompted the overgrowth of primary follicles in sugar-fed Ae. aegypti females but blocked the development of primary follicles at Christopher’s Stage III after blood feeding. Secondary follicles were precociously activated in PPF-treated mosquitoes. Moreover, PPF substantially altered the expression of many genes that are essential for mosquito physiology and oocyte development in the fat body and ovary. In particular, many metabolic genes were differentially expressed in response to PPF treatment, thereby affecting the mobilization and utilization of energy reserves. Furthermore, PPF treatment on the previtellogenic female adults considerably modified mosquito responses to JH and 20-hydroxyecdysone (20E), two major hormones that govern mosquito reproduction. Krüppel homolog 1, a JH-inducible transcriptional regulator, showed consistently elevated expression after PPF exposure. Conversely, PPF upregulated the expression of several key players of the 20E regulatory cascades, including HR3 and E75A, in the previtellogenic stage. After blood-feeding, the expression of these 20E response genes was significantly weaker in PPF-treated mosquitoes than the solvent-treated control groups. RNAi-mediated knockdown of the Methoprene-tolerant (Met) protein, the JH receptor, partially rescued the impaired follicular development after PPF exposure and substantially increased the hatching of the eggs produced by PPF-treated female mosquitoes. Thus, the results suggested that PPF relied on Met to exert its sterilizing effects on female mosquitoes. In summary, this study finds that PPF exposure disturbs normal hormonal responses and metabolism in Ae. aegypti, shedding light on the molecular targets and the downstream signaling pathways activated by PPF.Author summaryAedes aegypti mosquitoes are responsible for the transmission of dengue, yellow fever, chikungunya, and Zika fever. Insecticides are widely used as the primary tool in the prevention and control of these infectious diseases. In light of the rapid increase of insecticide resistance in mosquito populations, there is an urgent need to find new classes of insecticides with a different mode of action. Here we found that pyriproxyfen, an analog of insect juvenile hormone (JH), had a large impact on the oocyte development, both before and after blood feeding, in female mosquitoes. Pyriproxyfen disturbed normal hormonal responses and caused metabolic shifting in female adults. These actions appear to collectively impair oocyte development and substantially reduce viable progenies of female mosquitoes. Besides, we demonstrated the involvement of the JH receptor Met in pyriproxyfen-induced female sterilization. This study significantly advances our understanding of mosquito reproductive biology and the molecular basis of pyriproxyfen action, which are invaluable for the development of new mosquito control strategies.

scholarly journals Mating and blood-feeding induce transcriptome changes in the spermathecae of the yellow fever mosquito Aedes aegypti

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Carolina Camargo ◽  
Yasir H. Ahmed-Braimah ◽  
I. Alexandra Amaro ◽  
Laura C. Harrington ◽  
Mariana F. Wolfner ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Blood Meal ◽  
Transcriptional Response ◽  
Blood Feeding ◽  
Sperm Storage ◽  
Biological Processes ◽  
Gene Products ◽  
Heme Peroxidase ◽  
Males And Females

Abstract Aedes aegypti mosquitoes are the primary vectors of numerous viruses that impact human health. As manipulation of reproduction has been proposed to suppress mosquito populations, elucidation of biological processes that enable males and females to successfully reproduce is necessary. One essential process is female sperm storage in specialized structures called spermathecae. Aedes aegypti females typically mate once, requiring them to maintain sperm viably to fertilize eggs they lay over their lifetime. Spermathecal gene products are required for Drosophila sperm storage and sperm viability, and a spermathecal-derived heme peroxidase is required for long-term Anopheles gambiae fertility. Products of the Ae. aegypti spermathecae, and their response to mating, are largely unknown. Further, although female blood-feeding is essential for anautogenous mosquito reproduction, the transcriptional response to blood-ingestion remains undefined in any reproductive tissue. We conducted an RNAseq analysis of spermathecae from unfed virgins, mated only, and mated and blood-fed females at 6, 24, and 72 h post-mating and identified significant differentially expressed genes in each group at each timepoint. A blood-meal following mating induced a greater transcriptional response in the spermathecae than mating alone. This study provides the first view of elicited mRNA changes in the spermathecae by a blood-meal in mated females.

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.

THE DIGESTIVE PROCESSES OF HAEMATOPHAGOUS INSECTS: IV. SECRETION OF TRYPSIN BY AEDES AEGYPTI (DIPTERA: CULICIDAE)

1973 ◽  
Vol 105 (4) ◽  
pp. 599-603 ◽  
Author(s):  
R. H. Gooding
Keyword(s):  
Amino Acids ◽  
Tissue Culture ◽  
Aedes Aegypti ◽  
Blood Meal ◽  
Culture Medium ◽  
Tissue Culture Medium ◽  
Trypsin Activity ◽  
Chymotrypsin Activity ◽  
Digestive Processes

AbstractThere is a correlation between the amount of blood ingested by Aedes aegypti (L.) and the trypsin activity (but not the chymotrypsin activity) in the midgut 16 and 24 hr after feeding. Puromycin and Dactinomycin ingested with a blood meal depress the level of midgut trypsin. Trypsin purified from the midguts of A. aegypti fed upon defibrinated blood containing 14C-amino acids contains radioactivity. Midguts from blood-fed mosquitoes did not produce significant amounts of trypsin when dissected from mosquitoes and maintained in a tissue culture medium for up to 50 hr.

THE EFFECT OF NUTRIENT INTAKE ON THE DEVELOPMENT AND THE EGG PRODUCTION OF RHODNIUS PROLIXUS STÅHL (HEMIPTERA: REDUVIIDAE)

1965 ◽  
Vol 43 (6) ◽  
pp. 891-904 ◽  
Author(s):  
W. G. Friend ◽  
C. T. H. Choy ◽  
E. Cartwright
Keyword(s):  
Body Weight ◽  
Blood Meal ◽  
Nutrient Intake ◽  
Egg Production ◽  
Abdominal Distension ◽  
Rhodnius Prolixus ◽  
The Body ◽  
Single Meal ◽  
Time Required ◽  
High Level

Nymphs of Rhodnius prolixus usually take a meal that is nine times the body weight before feeding. Adults usually take only three times their body weight as a blood meal. During the first 24 hours after feeding, the insect eliminates over 40% of the weight of the blood meal as dilute urine. The weight loss after this period is much more gradual.The minimum blood meal which promoted molting in various instars varied between 24.7 and 42.8% of the standard "maximum meal" for each instar; the minimum meal that promoted egg production was 31.3%. Limiting the size of the blood meal to these levels does not extend the time required for molting or egg production.Third- and fifth-instar nymphs, brought to a high level of nutrition by being fed a series of meals that are too small to cause molting, can be made to molt by a terminal meal that is about half the minimum single meal required to induce molting. Thus the amount of abdominal distension required to initiate molting can be lowered if the animals have been brought to a high level of nutrition.Up to a limit of 28 eggs, the number of eggs produced by a female shows good correlation with the amount of blood taken as food.

scholarly journals The impact of mating and sugar feeding on blood-feeding physiology and behavior in the arbovirus vector mosquito Aedes aegypti

2021 ◽  
Vol 15 (9) ◽  
pp. e0009815
Author(s):  
Garrett P. League ◽  
Ethan C. Degner ◽  
Sylvie A. Pitcher ◽  
Yassi Hafezi ◽  
Erica Tennant ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Blood Meal ◽  
Egg Production ◽  
Control Strategies ◽  
Blood Feeding ◽  
Female Behavior ◽  
Sugar Feeding ◽  
And Behavior ◽  
The Impact ◽  
Initial Blood

Background Aedes aegypti mosquitoes are globally distributed vectors of viruses that impact the health of hundreds of millions of people annually. Mating and blood feeding represent fundamental aspects of mosquito life history that carry important implications for vectorial capacity and for control strategies. Females transmit pathogens to vertebrate hosts and obtain essential nutrients for eggs during blood feeding. Further, because host-seeking Ae. aegypti females mate with males swarming near hosts, biological crosstalk between these behaviors could be important. Although mating influences nutritional intake in other insects, prior studies examining mating effects on mosquito blood feeding have yielded conflicting results. Methodology/Principal findings To resolve these discrepancies, we examined blood-feeding physiology and behavior in virgin and mated females and in virgins injected with male accessory gland extracts (MAG), which induce post-mating changes in female behavior. We controlled adult nutritional status prior to blood feeding by using water- and sugar-fed controls. Our data show that neither mating nor injection with MAG affect Ae. aegypti blood intake, digestion, or feeding avidity for an initial blood meal. However, sugar feeding, a common supplement in laboratory settings but relatively rare in nature, significantly affected all aspects of feeding and may have contributed to conflicting results among previous studies. Further, mating, MAG injection, and sugar intake induced declines in subsequent feedings after an initial blood meal, correlating with egg production and laying. Taking our evaluation to the field, virgin and mated mosquitoes collected in Colombia were equally likely to contain blood at the time of collection. Conclusions/Significance Mating, MAG, and sugar feeding impact a mosquito’s estimated ability to transmit pathogens through both direct and indirect effects on multiple aspects of mosquito biology. Our results highlight the need to consider natural mosquito ecology, including diet, when assessing their physiology and behavior in the laboratory.

scholarly journals Blood meal source and mixed blood-feeding influence gut bacterial community composition in Aedes aegypti

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ephantus J. Muturi ◽  
Teresia M. Njoroge ◽  
Christopher Dunlap ◽  
Carla E. Cáceres
Keyword(s):  
Bacterial Community ◽  
Aedes Aegypti ◽  
Gut Microbiota ◽  
Microbial Communities ◽  
Blood Meal ◽  
Host Species ◽  
Bacterial Community Composition ◽  
Blood Feeding ◽  
Mixed Blood ◽  
Blood Meals

Abstract Background The guts of blood-sucking insects host a community of bacteria that can shift dramatically in response to biotic and abiotic factors. Identifying the key factors structuring these microbial communities has important ecological and epidemiological implications. Methods We used the yellow fever mosquito, Aedes aegypti, to investigate the impact of mixed blood meals on gut microbiota of vector mosquitoes. Adult females were experimentally fed on sugar or blood from chicken, rabbit or a mixture of chicken and rabbit blood, and their gut microbiota were characterized using 16S rRNA gene amplification and MiSeq sequencing. Results The gut bacterial communities of mosquitoes fed on the three blood meal treatments clustered separately, suggesting that host species identity and mixed blood-feeding are key determinants of gut bacterial community composition in mosquitoes. Mixed blood meal had a synergistic effect on both operational taxonomic unit (OTU) richness and the Shannon diversity index, suggesting that mixed blood-feeding can offset the nutritional deficit of blood meals from certain host species. The microbial communities observed in this study were distinct from those identified from similarly fed Ae. aegypti from our previous study. Conclusions These findings demonstrate that vector host-feeding preferences can influence gut microbial composition and diversity, which could potentially impact pathogen acquisition and transmission by the vector. The results also demonstrate that different microenvironmental conditions within the laboratory may play an important role in structuring the microbial communities of independently reared mosquito colonies.

scholarly journals Heterogeneity of midgut cells and their differential responses to blood meal ingestion by the mosquito, Aedes aegypti

2020 ◽  
Author(s):  
Yingjun Cui ◽  
Alexander W.E. Franz
Keyword(s):  
Aedes Aegypti ◽  
Blood Meal ◽  
Mosquito Species ◽  
Cell Types ◽  
Blood Feeding ◽  
Nutrient Absorption ◽  
Cell Type ◽  
Blood Digestion ◽  
Mosquito Midgut ◽  
Meal Ingestion

AbstractMosquitoes are the most notorious hematophagous insects and due to their blood feeding behavior and genetic compatibility, numerous mosquito species are highly efficient vectors for certain human pathogenic parasites and viruses. The mosquito midgut is the principal organ of blood meal digestion and nutrient absorption. It is also the initial site of infection with blood meal acquired parasites and viruses. We conducted an analysis based on single-nucleus RNA sequencing (snRNA-Seq) to assess the cellular diversity of the midgut and how individual cells respond to blood meal ingestion to facilitate its digestion. Our study revealed the presence of 20 distinguishable cell-type clusters in the female midgut of Aedes aegypti. The identified cell types included intestinal stem cell (ISC), enteroblasts (EB), differentiating EB (dEB), enteroendocrine cells (EE), enterocytes (EC), EC-like cells, cardia cells, and visceral muscle (VM) cells. Blood meal ingestion dramatically changed the overall midgut cell type composition, profoundly increasing the proportions of ISC and three EC/EC like clusters. In addition, transcriptional profiles of all cell types were strongly affected while genes involved in various metabolic processes were significantly upregulated. Our study provides a basis for further physiological and molecular studies on blood digestion, nutrient absorption, and cellular homeostasis in the mosquito midgut.

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