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.

Urban Landscape Features Influence the Movement and Distribution of the Australian Container-Inhabiting Mosquito Vectors Aedes aegypti (Diptera: Culicidae) and Aedes notoscriptus (Diptera: Culicidae)

2019 ◽  
Author(s):  
Brendan J Trewin ◽  
Daniel E Pagendam ◽  
Myron P Zalucki ◽  
Jonathan M Darbro ◽  
Gregor J Devine ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Urban Landscape ◽  
Mosquito Control ◽  
Control Strategies ◽  
Oviposition Behavior ◽  
Gaussian Kernel ◽  
Mosquito Vectors ◽  
Landscape Features ◽  
Rainwater Tanks

Abstract Urban landscape features play an important role in the distribution and population spread of mosquito vectors. Furthermore, current insecticide and novel rear-and-release strategies for urban mosquito management rarely consider the spatial structure of the landscape when applying control practices. Here, we undertake a mark-recapture experiment to examine how urban features influence the movement and distribution of Australian container-inhabiting Aedes vectors. We pay attention to the role of semipermanent water storage containers, called rainwater tanks, and the influence of movement barriers, such as roads, on the spread and distribution of vector populations. Results suggest that Aedes aegypti (Linnaeus) (Diptera: Culicidae) were more likely to be captured around rainwater tanks, and that released males travel throughout residential blocks but do not cross roads. Conversely, female Aedes notoscriptus (Skuse) (Diptera: Culicidae) movement was uninhibited by roads and rainwater tanks did not influence female distribution or oviposition behavior. Using an isotropic Gaussian kernel framework, we show that vector movement is likely to be greater when applying a temporal effect, than when estimated by traditional methods. We conclude that a greater understanding on the role of urban features on vector movement will be important in the new age of rear-and-release mosquito control strategies, particularly those where estimations of movement are important for ensuring efficacy of application.

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 Current Status of Aedes aegypti Insecticide Resistance Development from Banjarmasin, Kalimantan, Indonesia

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
P. H. Hamid ◽  
V. I. Ninditya ◽  
J. Prastowo ◽  
A. Haryanto ◽  
A. Taubert ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Insecticide Resistance ◽  
Point Mutation ◽  
Mosquito Control ◽  
Control Strategies ◽  
Current Status ◽  
Resistance Development ◽  
Health Authorities ◽  
Public Health Authorities ◽  
High Level

Aedes aegypti represents the principal vector of many arthropod-borne diseases in tropical areas worldwide. Since mosquito control strategies are mainly based on use of insecticides, resistance development can be expected to occur in frequently exposed Ae. aegypti populations. Surveillance on resistance development as well as testing of insecticide susceptibility is therefore mandatory and needs further attention by national/international public health authorities. In accordance, we here conducted a study on Ae. aegypti resistance development towards several often used insecticides, i.e., malathion, deltamethrin, permethrin, λ-cyhalothrin, bendiocarb, and cyfluthrin, in the periurban area of Banjarmasin city, Kalimantan, Indonesia. Our results clearly showed resistance development of Ae. aegypti populations against tested insecticides. Mortalities of Ae. aegypti were less than 90% with the highest resistance observed against 0.75% permethrin. Collected mosquitoes from Banjarmasin also presented high level of resistance development to 0.1% bendiocarb. Molecular analysis of voltage-gated sodium channel (Vgsc) gene showed significant association of V1016G gene point mutation in resistance Ae. aegypti phenotypes against 0.75% permethrin. However, F1534C gene point mutation did not correlate to Ae. aegypti insecticide resistance to 0.75% permethrin. Irrespective of periurban areas in Kalimantan considered as less densed island of Indonesia, Ae. aegypti-derived resistance to different routinely applied insecticides occurred. Our findings evidence that Ae. aegypti insecticide resistance is most likely spreading into less populated areas and thus needs further surveillance in order to delay Ae. aegypti resistance development.

scholarly journals The early gene Broad is involved in the ecdysteroid hierarchy governing vitellogenesis of the mosquito Aedes aegypti

2004 ◽  
Vol 33 (3) ◽  
pp. 743-761 ◽  
Author(s):  
L Chen ◽  
J Zhu ◽  
G Sun ◽  
A S Raikhel
Keyword(s):  
Aedes Aegypti ◽  
Fat Body ◽  
Regulatory Region ◽  
Blood Feeding ◽  
Early Gene ◽  
Gene Encoding ◽  
Obvious Effect ◽  
Early Genes ◽  
Old Females

The broad (br ) gene, encoding a family of C2H2 type zinc-finger DNA-binding proteins, has been shown to act as a crucial member of the 20-hydroxyecdysone (20E) regulatory hierarchy in the fruitfly, Drosophila melanogaster and the moth, Manduca sexta. In this study, we have shown that the br gene is involved in the 20E-regulatory hierarchy controlling vitellogenesis in the mosquito, Aedes aegypti. Unlike E74 and E75 early genes, expression of br was activated in previtellogenic females, during a juvenile hormone (JH)-dependent period. The levels of Z1, Z2 and Z4 isoform mRNA were elevated in the fat body of 2-day-old females after in vitro exposure to JH III. However, JH III repressed 20E activation of br in 3-to 5-day-old females, indicating a switch in hormonal commitment. Expression of Z1, Z2 and Z4 was stimulated after blood feeding in both vitellogenic tissues, the fat body and the ovary, corresponding to peaks of ecdysteroid titers. In the fat body, the mRNA profiles of these three isoforms correlated well with those of yolk protein precursor (YPP) genes. These BR isoforms were activated by 20E in fat bodies cultured in vitro and behaved as early genes, with a self-repressive autoregulatory loop that can be blocked by the protein inhibitor, cyclohexamide. Multiple binding sites for all four BR isoforms were present in the 5′-regulatory region of the major YPP gene, vitellogenin (Vg). Effects of BR isoforms on the expression of Vg have been demonstrated by cell transfection analysis. In particular, BR isoforms by themselves had no effects on the Vg promoter. However, Z1 and Z4 each repressed Aedes aegypti ecdysone receptor (EcR)/Ultraspiracle (USP)-mediated 20E activation of the Vg promoter, while Z2 enhanced activation of the Vg promoter by AaEcR/AaUSP in the presence of 20E. Z3 had no obvious effect in the same experiment. These results suggested that BR isoforms are essential for proper activation and termination of the Vg gene in response to 20E. Overall, our study implicated br in the regulation of mosquito vitellogenesis.

scholarly journals Human blood microRNA hsa-miR-21-5p induces vitellogenin in the mosquito Aedes aegypti

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hugo D. Perdomo ◽  
Mazhar Hussain ◽  
Rhys Parry ◽  
Kayvan Etebari ◽  
Lauren M. Hedges ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Human Blood ◽  
Egg Production ◽  
Fat Body ◽  
Blood Feeding ◽  
Mosquito Vectors ◽  
Progeny Production ◽  
Proteomics Analysis ◽  
Gene Coding ◽  
Reproductive Events

AbstractMosquito vectors transmit various diseases through blood feeding, required for their egg development. Hence, blood feeding is a major physiological event in their life cycle, during which hundreds of genes are tightly regulated. Blood is a rich source of proteins for mosquitoes, but also contains many other molecules including microRNAs (miRNAs). Here, we found that human blood miRNAs are transported abundantly into the fat body tissue of Aedes aegypti, a key metabolic center in post-blood feeding reproductive events, where they target and regulate mosquito genes. Using an artificial diet spiked with the mimic of an abundant and stable human blood miRNA, hsa-miR-21-5p, and proteomics analysis, we found over 40 proteins showing differential expression in female Ae. aegypti mosquitoes after feeding. Of interest, we found that the miRNA positively regulates the vitellogenin gene, coding for a yolk protein produced in the mosquito fat body and then transported to the ovaries as a protein source for egg production. Inhibition of hsa-miR-21-5p followed by human blood feeding led to a statistically insignificant reduction in progeny production. The results provide another example of the involvement of small regulatory molecules in the interaction of taxonomically vastly different taxa.

scholarly journals Workshop for priority-setting in Aedes aegypti control interventions in Latin America and the Caribbean: a policy dialogue

2019 ◽  
Vol 35 (4) ◽  
Author(s):  
Agustin Ciapponi ◽  
Ariel Bardach ◽  
Andrea Alcaraz ◽  
María Belizán ◽  
Daniel Jones ◽  
...  
Keyword(s):  
Latin America ◽  
Aedes Aegypti ◽  
Vector Control ◽  
Priority Setting ◽  
Mosquito Control ◽  
Control Strategies ◽  
Policy Dialogue ◽  
Regional Research ◽  
Deliberative Process ◽  
The Caribbean

This article presents the results of a dialogue between decision-makers and experts in Latin America and the Caribbean on priority-setting for interventions and studies on Aedes aegypti control. The article is part of a project that included a systematic review of mosquito control strategies and a qualitative study with key informants from the region. Using a collective deliberative process assisted by the results of the above-mentioned projects, a list of priorities was developed by consensus for the implementation of vector control strategies and the development of key regional research lines. It was agreed that the best strategy is integrated vector management, divided into: (a) chemical control; (b) biological control; (c) environmental management; (d) community participation; and (e) integrated surveillance. The workshop highlighted the crucial role of government leadership and inter-sector coordination between government agencies and civil society stakeholders. The proposed priorities for research lines were: Ae. aegypti vector competence and associated factors; community components of interventions; incorporation of technology into vector control and monitoring; most efficient modalities of integrated surveillance; entomological indicators with the best predictive capacity; and resistance to insecticides. The policy dialogue methodology allowed validating and enriching the results of other levels of research, besides establishing priorities for regional research and control strategies.

scholarly journals Juvenile hormone regulation of microRNAs is mediated by E75 in the Dengue vector mosquito Aedes aegypti

2021 ◽  
Vol 118 (29) ◽  
pp. e2102851118
Author(s):  
Emre Aksoy ◽  
Alexander S. Raikhel
Keyword(s):  
Aedes Aegypti ◽  
Juvenile Hormone ◽  
Fat Body ◽  
Mirna Gene ◽  
Luciferase Assay ◽  
Small Rna Sequencing ◽  
Hormone Regulation ◽  
Gene Target ◽  
Body Tissues

MicroRNAs (miRNAs) are small noncoding RNAs that play critical roles in controlling posttranscriptional gene regulation and have a profound effect on mosquito reproduction and metabolism. Juvenile hormone (JH) is critical for achieving reproductive competence in the main vector of human arboviral diseases, Aedes aegypti. We report a JH-mediated mechanism governing miRNA expression. Using a transcription factor screen with multiple primary miRNA (pri-miRNA) promoters, we identified that the Ecdysone-induced protein E75 (E75) isoform (E75-RD) induced miRNA gene promoter activity. E75 binding sites were determined in miRNA promoters by means of cell transfection assay. E75-RD was found to be up-regulated by JH, as shown by the JH application and RNA interference (RNAi) of the JH receptor Methoprene-tolerant (Met). Small RNA sequencing from RNAi of Met and E75 displayed an overlapping miRNA cohort, suggesting E75 to be an intermediate component within the JH hierarchical network controlling miRNAs. Further experiments confirmed that E75-RD positively regulates several miRNAs including miR-2940. Reducing miR-2940 resulted in the arrest of follicle development and number of eggs laid. Performing miRNA target predictions and RT-qPCR from antagomir Ant-2940-3p–treated fat body tissues identified the mRNA target Clumsy (AAEL002518). The molecular interaction between this gene target and miR-2940 was confirmed using an in vitro dual luciferase assay in Drosophila S2 cells and in Ae. aegypti Aag2 cell lines. Finally, we performed a phenotypic rescue experiment to demonstrate that miR-2940/Clumsy is responsible for the disruption in egg development. Collectively, these results established the role of JH-mediated E75-RD in regulation of miRNA gene expression during the mosquito reproductive cycle.

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