Browsing by Subject "Aedes"

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    Assessment of Trinidad community stakeholder perspectives on the use of yeast interfering RNA-baited ovitraps for biorational control of Aedes mosquitoes
    (PLOS, 2021-06-29) Winter, Nikhella; Stewart, Akilah T.M.; Igiede, Jessica; Wiltshire, Rachel M.; Hapairai, Limb K.; James, Lester D.; Mohammed, Azad; Severson, David W.; Duman-Scheel, Molly; Medical and Molecular Genetics, School of Medicine
    Dengue, Zika, chikungunya and yellow fever viruses continue to be a major public health burden. Aedes mosquitoes, the primary vectors responsible for transmitting these viral pathogens, continue to flourish due to local challenges in vector control management. Yeast interfering RNA-baited larval lethal ovitraps are being developed as a novel biorational control tool for Aedes mosquitoes. This intervention circumvents increasing issues with insecticide resistance and poses no known threat to non-target organisms. In an effort to create public awareness of this alternative vector control strategy, gain stakeholder feedback regarding product design and acceptance of the new intervention, and build capacity for its potential integration into existing mosquito control programs, this investigation pursued community stakeholder engagement activities, which were undertaken in Trinidad and Tobago. Three forms of assessment, including paper surveys, community forums, and household interviews, were used with the goal of evaluating local community stakeholders' knowledge of mosquitoes, vector control practices, and perceptions of the new technology. These activities facilitated evaluation of the hypothesis that the ovitraps would be broadly accepted by community stakeholders as a means of biorational control for Aedes mosquitoes. A comparison of the types of stakeholder input communicated through use of the three assessment tools highlighted the utility and merit of using each tool for assessing new global health interventions. Most study participants reported a general willingness to purchase an ovitrap on condition that it would be affordable and safe for human health and the environment. Stakeholders provided valuable input on product design, distribution, and operation. A need for educational campaigns that provide a mechanism for educating stakeholders about vector ecology and management was highlighted. The results of the investigation, which are likely applicable to many other Caribbean nations and other countries with heavy arboviral disease burdens, were supportive of supplementation of existing vector control strategies through the use of the yeast RNAi-based ovitraps.
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    Characterization of an adulticidal and larvicidal interfering RNA pesticide that targets a conserved sequence in mosquito G protein-coupled dopamine 1 receptor genes
    (Elsevier, 2020) Hapairai, Limb K.; Mysore, Keshava; Sun, Longhua; Li, Ping; Wang, Chien-Wei; Scheel, Nicholas D.; Lesnik, Alexandra; Scheel, Max P.; Igiede, Jessica; Wei, Na; Severson, David W.; Duman-Scheel, Molly; Medical and Molecular Genetics, School of Medicine
    G protein-coupled receptors (GPCRs), key regulators of a variety of critical biological processes, are attractive targets for insecticide development. Given the importance of these receptors in many organisms, including humans, it is critical that novel pesticides directed against GPCRs are designed to be species-specific. Here, we present characterization of an interfering RNA pesticide (IRP) targeting the mosquito GPCR-encoding dopamine 1 receptor (dop1) genes. A small interfering RNA corresponding to dop1 was identified in a screen for IRPs that kill Aedes aegypti during both the adult and larval stages. The 25 bp sequence targeted by this IRP is conserved in the dop1 genes of multiple mosquito species, but not in non-target organisms, indicating that it could function as a biorational mosquito insecticide. Aedes aegypti adults treated through microinjection or attractive toxic sugar bait delivery of small interfering RNA corresponding to the target site exhibited severe neural and behavioral defects and high levels of adult mortality. Likewise, A. aegypti larval consumption of dried inactivated yeast tablets prepared from a Saccharomyces cerevisiae strain engineered to express short hairpin RNA corresponding to the dop1 target site resulted in severe neural defects and larval mortality. Aedes albopictus and Anopheles gambiae adult and larval mortality was also observed following treatment with dop1 IRPs, which were not toxic to non-target arthropods. The results of this investigation indicate that dop1 IRPs can be used for species-specific targeting of dop1 GPCRs and may represent a new biorational strategy for control of both adult and larval mosquitoes.
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    Chitosan/siRNA nanoparticle targeting demonstrates a requirement for single-minded during larval and pupal olfactory system development of the vector mosquito Aedes aegypti
    (Springer Nature, 2014-02-19) Mysore, Keshava; Andrews, Emily; Li, Ping; Duman-Scheel, Molly; Medical and Molecular Genetics, School of Medicine
    Background: Essentially nothing is known about the genetic regulation of olfactory system development in vector mosquitoes, which use olfactory cues to detect blood meal hosts. Studies in Drosophila melanogaster have identified a regulatory matrix of transcription factors that controls pupal/adult odorant receptor (OR) gene expression in olfactory receptor neurons (ORNs). However, it is unclear if transcription factors that function in the D. melanogaster regulatory matrix are required for OR expression in mosquitoes. Furthermore, the regulation of OR expression during development of the larval olfactory system, which is far less complex than that of pupae/adults, is not well understood in any insect, including D. melanogaster. Here, we examine the regulation of OR expression in the developing larval olfactory system of Aedes aegypti, the dengue vector mosquito. Results: A. aegypti bears orthologs of eight transcription factors that regulate OR expression in D. melanogaster pupae/adults. These transcription factors are expressed in A. aegypti larval antennal sensory neurons, and consensus binding sites for these transcription factors reside in the 5' flanking regions of A. aegypti OR genes. Consensus binding sites for Single-minded (Sim) are located adjacent to over half the A. aegypti OR genes, suggesting that this transcription factor functions as a major regulator of mosquito OR expression. To functionally test this hypothesis, chitosan/siRNA nanoparticles were used to target sim during larval olfactory development. These experiments demonstrated that Sim positively regulates expression of a large subset of OR genes, including orco, the obligate co-receptor in the assembly and function of heteromeric OR/Orco complexes. Decreased innervation of the antennal lobe was also noted in sim knockdown larvae. These OR expression and antennal lobe defects correlated with a larval odorant tracking behavioral defect. OR expression and antennal lobe defects were also observed in sim knockdown pupae. Conclusions: The results of this investigation indicate that Sim has multiple functions during larval and pupal olfactory system development in A. aegypti.
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    Disruption of Aedes aegypti Olfactory System Development through Chitosan/siRNA Nanoparticle Targeting of semaphorin-1a
    (Public Library of Science, 2013-05-16) Mysore, Keshava; Flannery, Ellen M.; Tomchaney, Michael; Severson, David W.; Duman-Scheel, Molly; Medical and Molecular Genetics, School of Medicine
    Despite the devastating impact of mosquito-borne illnesses on human health, surprisingly little is known about mosquito developmental biology, including development of the olfactory system, a tissue of vector importance. Analysis of mosquito olfactory developmental genetics has been hindered by a lack of means to target specific genes during the development of this sensory system. In this investigation, chitosan/siRNA nanoparticles were used to target semaphorin-1a (sema1a) during olfactory system development in the dengue and yellow fever vector mosquito Aedes aegypti. Immunohistochemical analyses and anterograde tracing of antennal sensory neurons, which were used to track the progression of olfactory development in this species, revealed antennal lobe defects in sema1a knockdown fourth instar larvae. These findings, which correlated with a larval odorant tracking behavioral phenotype, identified previously unreported roles for Sema1a in the developing insect larval olfactory system. Analysis of sema1a knockdown pupae also revealed a number of olfactory phenotypes, including olfactory receptor neuron targeting and projection neuron defects coincident with a collapse in the structure and shape of the antennal lobe and individual glomeruli. This study, which is to our knowledge the first functional genetic analysis of insect olfactory development outside of D. melanogaster, identified critical roles for Sema1a during Ae. aegypti larval and pupal olfactory development and advocates the use of chitosan/siRNA nanoparticles as an effective means of targeting genes during post-embryonic Ae. aegypti development. Use of siRNA nanoparticle methodology to understand sensory developmental genetics in mosquitoes will provide insight into the evolutionary conservation and divergence of key developmental genes which could be exploited in the development of both common and species-specific means for intervention.
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    Infectious disease risks at the Rugby World Cup 2023 in France - Beware of Aedes and co!
    (Elsevier, 2023-09-09) Al-Tawfiq, Jaffar A.; Hedrich, Nadja; Lovey, Thibault; Gautret, Philippe; Schlagenhauf, Patricia; Medicine, School of Medicine
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    Maximizing the Potential of Attractive Targeted Sugar Baits (ATSBs) for Integrated Vector Management
    (MDPI, 2023-06-28) Njoroge, Teresia Muthoni; Hamid-Adiamoh, Majidah; Duman-Scheel, Molly; Medical and Molecular Genetics, School of Medicine
    Due to the limitations of the human therapeutics and vaccines available to treat and prevent mosquito-borne diseases, the primary strategy for disease mitigation is through vector control. However, the current tools and approaches used for mosquito control have proven insufficient to prevent malaria and arboviral infections, such as dengue, Zika, and lymphatic filariasis, and hence, these diseases remain a global public health threat. The proven ability of mosquito vectors to adapt to various control strategies through insecticide resistance, invasive potential, and behavioral changes from indoor to outdoor biting, combined with human failures to comply with vector control requirements, challenge sustained malaria and arboviral disease control worldwide. To address these concerns, increased efforts to explore more varied and integrated control strategies have emerged. These include approaches that involve the behavioral management of vectors. Attractive targeted sugar baits (ATSBs) are a vector control approach that manipulates and exploits mosquito sugar-feeding behavior to deploy insecticides. Although traditional approaches have been effective in controlling malaria vectors indoors, preventing mosquito bites outdoors and around human dwellings is challenging. ATSBs, which can be used to curb outdoor biting mosquitoes, have the potential to reduce mosquito densities and clinical malaria incidence when used in conjunction with existing vector control strategies. This review examines the available literature regarding the utility of ATSBs for mosquito control, providing an overview of ATSB active ingredients (toxicants), attractants, modes of deployment, target organisms, and the potential for integrating ATSBs with existing vector control interventions.
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    Sugar-Baited Delivery of Small Interfering RNA for Gene Silencing in Adult Mosquitoes
    (Cold Spring Harbor Laboratory, 2022-07-12) Mysore, Keshava; Hapairai, Limb; Realey, Jacob S.; Sun, Longhua; Roethele, Joseph B.; Duman-Scheel, Molly; Medical and Molecular Genetics, School of Medicine
    RNA interference (RNAi), an innate regulatory mechanism that is conserved across many eukaryotic species, has been harnessed for experimental gene silencing in many organisms, including mosquitoes. This protocol describes an optimized method for inducing RNAi in adult Aedes aegypti and Anopheles gambiae mosquitoes that involves feeding them a red-colored sugar bait containing small interfering RNA (siRNA). This oral delivery method is less physically disruptive than delivery by subcutaneous injection, and the use of siRNAs (in contrast to long dsRNAs) for RNAi enables the design of molecules that target conserved sites so that gene function can be studied in multiple species. After feeding, the behavioral and morbidity phenotypes that result from the suppression of target gene expression can then be analyzed.
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    Targeting Mosquitoes through Generation of an Insecticidal RNAi Yeast Strain Using Cas-CLOVER and Super PiggyBac Engineering in Saccharomyces cerevisiae
    (MDPI, 2023-10-27) Brizzee, Corey; Mysore, Keshava; Njoroge, Teresia M.; McConnell, Seth; Hamid-Adiamoh, Majidah; Stewart, Akilah T. M.; Kinder, J. Tyler; Crawford, Jack; Duman-Scheel, Molly; Medical and Molecular Genetics, School of Medicine
    The global deployment of RNAi yeast insecticides involves transitioning from the use of laboratory yeast strains to more robust strains that are suitable for scaled fermentation. In this investigation, the RNA-guided Cas-CLOVER system was used in combination with Piggybac transposase to produce robust Saccharomyces cerevisiae strains with multiple integrated copies of the Sh.463 short hairpin RNA (shRNA) insecticide expression cassette. This enabled the constitutive high-level expression of an insecticidal shRNA corresponding to a target sequence that is conserved in mosquito Shaker genes, but which is not found in non-target organisms. Top-expressing Cas-CLOVER strains performed well in insecticide trials conducted on Aedes, Culex, and Anopheles larvae and adult mosquitoes, which died following consumption of the yeast. Scaled fermentation facilitated the kilogram-scale production of the yeast, which was subsequently heat-killed and dried. These studies indicate that RNAi yeast insecticide production can be scaled, an advancement that may one day facilitate the global distribution of this new mosquito control intervention.