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Dr. George Dimopoulos
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA

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0 Genomics
0 Innate Immunity
0 Malaria
0 Metagenomics
0 Transcriptomics

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Malaria
<i>Anopheles gambiae</i>
Plasmodium
Dengue
<i>Aedes aegypti</i>
Malaria Control
Innate Immunity
Genomics
microbiome
Microflora
Dengue control

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Journal article
Published: 20 May 2021 in Developmental & Comparative Immunology
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Mosquito anti-pathogen immune responses, including those controlling infection with arboviruses are regulated by multiple signal transduction pathways. While the Toll pathway is critical in the defense against arboviruses such as dengue and Zika viruses, the factors and mechanisms involved in virus recognition leading to the activation of the Toll pathway are not fully understood. In this study we evaluated the role of virus-produced double-stranded RNA (dsRNA) intermediates in mosquito immune activation by utilizing the synthetic dsRNA analog polyinosinic-polycytidylic acid (poly I:C). Poly I:C treatment of Aedes aegypti mosquitoes and Aag2 cells reduced DENV infection. Transcriptomic analyses of Aag2 cell responses to poly I:C indicated putative activation of the Toll pathway. We found that poly I:C is translocated to the endosomal compartment of Aag2 cells, and that the A. aegypti Toll 6 receptor is a putative dsRNA recognition receptor. This study elucidates the role of dsRNAs in the immune activation of non-RNAi pathways in mosquitoes.

ACS Style

Yesseinia I. Angleró-Rodríguez; Chinmay V. Tikhe; Seokyoung Kang; George Dimopoulos. Aedes aegypti Toll pathway is induced through dsRNA sensing in endosomes. Developmental & Comparative Immunology 2021, 122, 104138 .

AMA Style

Yesseinia I. Angleró-Rodríguez, Chinmay V. Tikhe, Seokyoung Kang, George Dimopoulos. Aedes aegypti Toll pathway is induced through dsRNA sensing in endosomes. Developmental & Comparative Immunology. 2021; 122 ():104138.

Chicago/Turabian Style

Yesseinia I. Angleró-Rodríguez; Chinmay V. Tikhe; Seokyoung Kang; George Dimopoulos. 2021. "Aedes aegypti Toll pathway is induced through dsRNA sensing in endosomes." Developmental & Comparative Immunology 122, no. : 104138.

Article
Published: 08 May 2021
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Melanins are structurally complex pigments produced by organisms in all domains of life. In insects, melanins are essential for survival and have key roles in cuticle sclerotization, wound healing and innate immunity. In this study, we used a diverse set of molecular, biochemical, and imaging approaches to characterize mosquito melanin involved in innate immune defense (melanotic capsules). We observed that melanotic capsules enclosing Plasmodium berghei ookinetes were composed of an acid-resistant and highly hydrophobic material with granular appearance, which are characteristic properties of melanins. Spectroscopical analyses reveal chemical signatures of eumelanins and pheomelanin. Furthermore, we identified a set of 14 acid-resistant mosquito proteins embedded within the melanin matrix possibly related to an anti-Plasmodium response. Among these, AgMESH, a mucin-related protein highly conserved among insects that is associated with the midgut brush border microvilli proteome of Anopheles gambiae and A. albimanus. AgMESH gene silencing in mosquitos was associated with reduced Plasmodium parasite infection, compromised integrity of the peritrophic matrix, and inability to synthesize a dityrosine network. Our results provide a new approach to study aspects of insect melanogenesis that revealed proteins associated with melanotic capsule, one of which was strongly implicated in the stabilization of the peritrophic matrix and pathogenesis of Plasmodium spp. mosquito infection. Given the conservation of AgMESH among disease-transmitting insect vector species, future analysis of this protein could provide fertile ground for the identification of strategies that block transmission of vector borne diseases to humans. Significance Statement Malaria is a parasitic disease transmitted by mosquito bites. Here, we adapt methodologies to study fungal melanogenesis to explore the melanin-based immune response of Anopheles gambiae against malaria parasites. We reveal that melanotic capsules against Plasmodium are composed of pheomelanin and eumelanin. We demonstrate that melanin-encapsulated Plasmodium is associated to acid-resistant mosquito gut proteins and identify several putative factors of the melanin-mediated immunity. Disruption of AgMESH, a surface-associated protein conserved among other mosquito vectors, demonstrates its ability to impaired formation of the dityrosine network and peritrophic matrix compromising parasite development within the mosquito gut. Our study provides a new approach to investigate the melanin-based defense mechanism in insects and identified a potential host molecule for developing novel universal vector-control schemes.

ACS Style

Emma Camacho; Yuemei Dong; Yesseinia Anglero-Rodriguez; Daniel F. Q. Smith; Ricardo De Souza Jacomini; Scott A. McConnell; George Dimopoulos; Arturo Casadevall. AgMESH, a peritrophic matrix-associated protein embedded in Anopheles gambiae melanotic capsules modulates malaria parasite infection. 2021, 1 .

AMA Style

Emma Camacho, Yuemei Dong, Yesseinia Anglero-Rodriguez, Daniel F. Q. Smith, Ricardo De Souza Jacomini, Scott A. McConnell, George Dimopoulos, Arturo Casadevall. AgMESH, a peritrophic matrix-associated protein embedded in Anopheles gambiae melanotic capsules modulates malaria parasite infection. . 2021; ():1.

Chicago/Turabian Style

Emma Camacho; Yuemei Dong; Yesseinia Anglero-Rodriguez; Daniel F. Q. Smith; Ricardo De Souza Jacomini; Scott A. McConnell; George Dimopoulos; Arturo Casadevall. 2021. "AgMESH, a peritrophic matrix-associated protein embedded in Anopheles gambiae melanotic capsules modulates malaria parasite infection." , no. : 1.

Journal article
Published: 28 April 2021 in mSphere
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Mosquitoes must blood feed multiple times to acquire and transmit malaria. However, the impact of an additional mosquito blood meal following malaria parasite infection has not been closely examined.

ACS Style

Hyeogsun Kwon; Maria L. Simões; Rebekah A. Reynolds; George Dimopoulos; Ryan C. Smith. Additional Feeding Reveals Differences in Immune Recognition and Growth of Plasmodium Parasites in the Mosquito Host. mSphere 2021, 6, 1 .

AMA Style

Hyeogsun Kwon, Maria L. Simões, Rebekah A. Reynolds, George Dimopoulos, Ryan C. Smith. Additional Feeding Reveals Differences in Immune Recognition and Growth of Plasmodium Parasites in the Mosquito Host. mSphere. 2021; 6 (2):1.

Chicago/Turabian Style

Hyeogsun Kwon; Maria L. Simões; Rebekah A. Reynolds; George Dimopoulos; Ryan C. Smith. 2021. "Additional Feeding Reveals Differences in Immune Recognition and Growth of Plasmodium Parasites in the Mosquito Host." mSphere 6, no. 2: 1.

Invertebrate microbiology
Published: 16 April 2021 in Microbial Ecology
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Mosquitoes, the major vectors of viruses like dengue, are naturally host to diverse microorganisms, which play an important role in their development, fecundity, immunity, and vector competence. The composition of their microbiota is strongly influenced by the environment, particularly their aquatic larval habitat. In this study, we used 2×300 bp 16s Illumina sequencing to compare the microbial profiles of emerging adult Aedes aegypti mosquitoes and the water collected from common types of aquatic habitat containers in Puerto Rico, which has endemic dengue transmission. We sequenced 141 mosquito and 46 water samples collected from plastic containers, septic tanks, discarded tires, underground trash cans, tree holes, or water meters. We identified 9 bacterial genera that were highly prevalent in the mosquito microbiome, and 77 for the microbiome of the aquatic habitat. The most abundant mosquito-associated bacterial OTUs were from the families Burkholderiaceae, Pseudomonadaceae, Comamonadaceae, and Xanthomonadaceae. Microbial profiles varied greatly between mosquitoes, and there were few major differences explained by container type; however, the microbiome of mosquitoes from plastic containers was more diverse and contained more unique taxa than the other groups. Container water was significantly more diverse than mosquitoes, and our data suggest that mosquitoes filter out many bacteria, with Alphaproteobacteria in particular being far more abundant in water. These findings provide novel insight into the microbiome of mosquitoes in the region and provide a platform to improve our understanding of the fundamental mosquito-microbe interactions.

ACS Style

E. P. Caragata; L. M. Otero; C. V. Tikhe; R. Barrera; G. Dimopoulos. Microbial Diversity of Adult Aedes aegypti and Water Collected from Different Mosquito Aquatic Habitats in Puerto Rico. Microbial Ecology 2021, 1 -20.

AMA Style

E. P. Caragata, L. M. Otero, C. V. Tikhe, R. Barrera, G. Dimopoulos. Microbial Diversity of Adult Aedes aegypti and Water Collected from Different Mosquito Aquatic Habitats in Puerto Rico. Microbial Ecology. 2021; ():1-20.

Chicago/Turabian Style

E. P. Caragata; L. M. Otero; C. V. Tikhe; R. Barrera; G. Dimopoulos. 2021. "Microbial Diversity of Adult Aedes aegypti and Water Collected from Different Mosquito Aquatic Habitats in Puerto Rico." Microbial Ecology , no. : 1-20.

Review
Published: 14 January 2021 in Viruses
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Mosquito-borne arthropod-borne viruses (arboviruses) such as the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are important human pathogens that are responsible for significant global morbidity and mortality. The recent emergence and re-emergence of mosquito-borne viral diseases (MBVDs) highlight the urgent need for safe and effective vaccines, therapeutics, and vector-control approaches to prevent MBVD outbreaks. In nature, arboviruses circulate between vertebrate hosts and arthropod vectors; therefore, disrupting the virus lifecycle in mosquitoes is a major approach for combating MBVDs. Several strategies were proposed to render mosquitoes that are refractory to arboviral infection, for example, those involving the generation of genetically modified mosquitoes or infection with the symbiotic bacterium Wolbachia. Due to the recent development of high-throughput screening methods, an increasing number of drugs with inhibitory effects on mosquito-borne arboviruses in mammalian cells were identified. These antivirals are useful resources that can impede the circulation of arboviruses between arthropods and humans by either rendering viruses more vulnerable in humans or suppressing viral infection by reducing the expression of host factors in mosquitoes. In this review, we summarize recent advances in small-molecule antiarboviral drugs in mammalian and mosquito cells, and discuss how to use these antivirals to block the transmission of MBVDs.

ACS Style

Shengzhang Dong; George Dimopoulos. Antiviral Compounds for Blocking Arboviral Transmission in Mosquitoes. Viruses 2021, 13, 108 .

AMA Style

Shengzhang Dong, George Dimopoulos. Antiviral Compounds for Blocking Arboviral Transmission in Mosquitoes. Viruses. 2021; 13 (1):108.

Chicago/Turabian Style

Shengzhang Dong; George Dimopoulos. 2021. "Antiviral Compounds for Blocking Arboviral Transmission in Mosquitoes." Viruses 13, no. 1: 108.

Review article
Published: 07 December 2020 in Developmental & Comparative Immunology
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Mosquitoes are vectors of a large number of viral pathogens. In recent years, increased urbanization and climate change has expanded the range of many vector mosquitoes. The lack of effective medical interventions has made the control of mosquito-borne viral diseases very difficult. Understanding the interactions between the mosquito immune system and viruses is critical if we are to develop effective control strategies against these diseases. Mosquitoes harbor multiple conserved immune pathways that curb invading viral pathogens. Despite the conservation of these pathways, the activation and intensity of the mosquito immune response varies with the mosquito species, tissue, and the infecting virus. This article reviews major conserved antiviral immune pathways in vector mosquitoes, their interactions with invading viral pathogens, and how these interactions restrict or promote infection of these medically important viruses.

ACS Style

Chinmay V. Tikhe; George Dimopoulos. Mosquito antiviral immune pathways. Developmental & Comparative Immunology 2020, 116, 103964 .

AMA Style

Chinmay V. Tikhe, George Dimopoulos. Mosquito antiviral immune pathways. Developmental & Comparative Immunology. 2020; 116 ():103964.

Chicago/Turabian Style

Chinmay V. Tikhe; George Dimopoulos. 2020. "Mosquito antiviral immune pathways." Developmental & Comparative Immunology 116, no. : 103964.

Research article
Published: 23 October 2020 in PLOS Neglected Tropical Diseases
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Prostaglandins (PGs) are immuno-active lipids that mediate the immune response in invertebrates and vertebrates. In insects, PGs play a role on different physiological processes such as reproduction, ion transport and regulation of cellular immunity. However, it is unclear whether PGs play a role in invertebrate's humoral immunity, and, if so, which immune signaling pathways would be modulated by PGs. Here, we show that Aedes aegypti gut microbiota and Gram-negative bacteria challenge induces prostaglandin production sensitive to an irreversible inhibitor of the vertebrate cyclooxygenase, acetylsalicylic acid (ASA). ASA treatment reduced PG synthesis and is associated with decreased expression of components of the Toll and IMD immune pathways, thereby rendering mosquitoes more susceptible to both bacterial and viral infections. We also shown that a cytosolic phospholipase (PLAc), one of the upstream regulators of PG synthesis, is induced by the microbiota in the midgut after blood feeding. The knockdown of the PLAc decreased prostaglandin production and enhanced the replication of Dengue in the midgut. We conclude that in Ae. aegypti, PGs control the amplitude of the immune response to guarantee an efficient pathogen clearance. Mosquito immune responses work on an on/off switch model, where the recognition of microorganisms turns the switch on, and its clearance turns it off. Besides pathogen derived molecules, no other compounds are known to directly regulate the activation and the amplitude of immune responses. Here we described that prostaglandins, lipid mediators of the immunity in vertebrates, also modulate the amplitude of immune responses in mosquitoes as well. Prostaglandins regulate the production of antimicrobial peptides and other effector molecules and directly impact the susceptibility of mosquitoes to bacterial and viral infections. When prostaglandin production is impaired, immune activation is inefficient and renders the mosquito more susceptible to bacterial and Dengue infections.

ACS Style

Ana Beatriz Ferreira Barletta; Thiago Luiz Alves E Silva; Octavio A. C. Talyuli; Tatiana Luna-Gomes; Shuzhen Sim; Yesseinia Angleró-Rodríguez; George Dimopoulos; Christianne Bandeira-Melo; Marcos H. Ferreira Sorgine. Prostaglandins regulate humoral immune responses in Aedes aegypti. PLOS Neglected Tropical Diseases 2020, 14, e0008706 .

AMA Style

Ana Beatriz Ferreira Barletta, Thiago Luiz Alves E Silva, Octavio A. C. Talyuli, Tatiana Luna-Gomes, Shuzhen Sim, Yesseinia Angleró-Rodríguez, George Dimopoulos, Christianne Bandeira-Melo, Marcos H. Ferreira Sorgine. Prostaglandins regulate humoral immune responses in Aedes aegypti. PLOS Neglected Tropical Diseases. 2020; 14 (10):e0008706.

Chicago/Turabian Style

Ana Beatriz Ferreira Barletta; Thiago Luiz Alves E Silva; Octavio A. C. Talyuli; Tatiana Luna-Gomes; Shuzhen Sim; Yesseinia Angleró-Rodríguez; George Dimopoulos; Christianne Bandeira-Melo; Marcos H. Ferreira Sorgine. 2020. "Prostaglandins regulate humoral immune responses in Aedes aegypti." PLOS Neglected Tropical Diseases 14, no. 10: e0008706.

Journal article
Published: 24 September 2020 in Parasites & Vectors
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Background Surveillance of mosquito infection status is critical for planning and deployment of proper mosquito control initiatives. Point-of-care (POC) detection assays are necessary for monitoring the infection prevalence and geographical range of viruses in mosquito vector populations. We therefore assessed the novel real-time PCR (qPCR) bCUBE (Hyris, London, UK) molecular diagnostic system as a tool for virus detection. Methods Aedes aegypti Rps17 was used to validate and determine correlation coefficient for the novel bCUBE qPCR system to a laboratory standard StepOnePlus real-time PCR system (Applied Biosystems, Waltham, MA, USA). Experimentally infected Ae. aegypti were quantified for Zika (ZIKV) and dengue virus serotype 2 (DENV2) viral genomic RNA. Infection prevalence was compared to plaque assay. Results We developed and validated a novel qPCR system for the detection of ZIKV and DENV2 using the real-time qPCR system bCUBE. With bCUBE-based qRT-PCR, viral genomic RNA could be detected in individually infected Ae. aegypti mosquitoes and in pools of 5, 10 or 15 mosquitoes. Conclusions The portable qPCR bCUBE diagnostic system is capable of detecting Zika and dengue virus in mosquitoes and therefore has potential as a practical field-deployable diagnostic test for vector-borne disease surveillance programmes.

ACS Style

Natalie Rutkowski; Yuemei Dong; George Dimopoulos. Field-deployable molecular diagnostic platform for arbovirus detection in Aedes aegypti. Parasites & Vectors 2020, 13, 1 -14.

AMA Style

Natalie Rutkowski, Yuemei Dong, George Dimopoulos. Field-deployable molecular diagnostic platform for arbovirus detection in Aedes aegypti. Parasites & Vectors. 2020; 13 (1):1-14.

Chicago/Turabian Style

Natalie Rutkowski; Yuemei Dong; George Dimopoulos. 2020. "Field-deployable molecular diagnostic platform for arbovirus detection in Aedes aegypti." Parasites & Vectors 13, no. 1: 1-14.

Article
Published: 25 August 2020 in mBio
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Understanding which mosquito species transmit an emerging arbovirus is critical to effective vector control. During the Zika virus epidemic in 2015 to 2016, Aedes mosquitoes were confirmed as vectors. However, studies addressing the vector status of Culex quinquefasciatus mosquitoes presented conflicting evidence and remain an outstanding source of confusion in the field. Here, we established a robust cell-based assay to identify infectious titers of Zika virus and assessed the virus titers in C. quinquefasciatus by quantitative real-time PCR (qRT-PCR). We found that while low levels of virus were detected in C. quinquefasciatus , these titers did not correspond to infectious virus, and these mosquitoes did not transmit virus in the saliva. We also present evidence that the virus may enter Culex cells before infection is disrupted. Our findings are important for future studies incriminating vector species using qRT-PCR for virus detection and offer new information on how virus transmission is blocked by mosquitoes.

ACS Style

Hannah J. MacLeod; George Dimopoulos. Detailed Analyses of Zika Virus Tropism in Culex quinquefasciatus Reveal Systemic Refractoriness. mBio 2020, 11, 1 .

AMA Style

Hannah J. MacLeod, George Dimopoulos. Detailed Analyses of Zika Virus Tropism in Culex quinquefasciatus Reveal Systemic Refractoriness. mBio. 2020; 11 (4):1.

Chicago/Turabian Style

Hannah J. MacLeod; George Dimopoulos. 2020. "Detailed Analyses of Zika Virus Tropism in Culex quinquefasciatus Reveal Systemic Refractoriness." mBio 11, no. 4: 1.

Preprint content
Published: 20 May 2020
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Melanin, a black-brown pigment found throughout all kingdoms of life, has diverse biological functions including: UV protection, thermoregulation, oxidant scavenging, arthropod immunity, and microbial virulence. Given melanin’s broad roles in the biosphere, particularly in insect immune defenses, it is important to understand how exposure to ubiquitous environmental contaminants affects melanization. Glyphosate – the most widely used herbicide globally – inhibits melanin production, which could have wide-ranging implications in the health of many organisms, including insects. Here, we demonstrate that glyphosate has deleterious effects on insect health in two evolutionary distant species, Galleria mellonella (Lepidoptera: Pyralidae) and Anopheles gambiae (Diptera: Culicidae), suggesting a broad effect in insects. Glyphosate reduced survival of G. mellonella caterpillars following infection with the fungus Cryptococcus neoformans and decreased the size of melanized nodules formed in hemolymph, which normally help eliminate infection. Glyphosate also increased the burden of the malaria- causing parasite Plasmodium falciparum in A. gambiae mosquitoes, altered uninfected mosquito survival, and perturbed the microbial composition of adult mosquito midguts. Our results show that glyphosate’s mechanism of melanin inhibition involves antioxidant synergy and disruption of the reaction oxidation-reduction balance Overall, these findings suggest that glyphosate’s environmental accumulation could render insects more susceptible to microbial pathogens due to melanin inhibition, immune impairment, and perturbations in microbiota composition, potentially contributing to declines in insect populations.

ACS Style

Daniel F. Q. Smith; Emma Camacho; Raviraj Thakur; Alexander J. Barron; Yuemei Dong; George Dimopoulos; Nichole A. Broderick; Arturo Casadevall. Glyphosate Inhibits Melanization and Increases Susceptibility to Infection in Insects. 2020, 1 .

AMA Style

Daniel F. Q. Smith, Emma Camacho, Raviraj Thakur, Alexander J. Barron, Yuemei Dong, George Dimopoulos, Nichole A. Broderick, Arturo Casadevall. Glyphosate Inhibits Melanization and Increases Susceptibility to Infection in Insects. . 2020; ():1.

Chicago/Turabian Style

Daniel F. Q. Smith; Emma Camacho; Raviraj Thakur; Alexander J. Barron; Yuemei Dong; George Dimopoulos; Nichole A. Broderick; Arturo Casadevall. 2020. "Glyphosate Inhibits Melanization and Increases Susceptibility to Infection in Insects." , no. : 1.

Journal article
Published: 15 May 2020 in Pathogens
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Mosquitoes can transmit many infectious diseases, such as malaria, dengue, Zika, yellow fever, and lymphatic filariasis. Current mosquito control strategies are failing to reduce the severity of outbreaks that still cause high human morbidity and mortality worldwide. Great expectations have been placed on genetic control methods. Among other methods, genetic modification of the bacteria colonizing different mosquito species and expressing anti-pathogen molecules may represent an innovative tool to combat mosquito-borne diseases. Nevertheless, this emerging approach, known as paratransgenesis, requires a detailed understanding of the mosquito microbiota and an accurate characterization of selected bacteria candidates. The acetic acid bacteria Asaia is a promising candidate for paratransgenic approaches. We have previously reported that Asaia symbionts play a beneficial role in the normal development of Anopheles mosquito larvae, but no study has yet investigated the role(s) of Asaia in adult mosquito biology. Here we report evidence on how treatment with a highly specific anti-Asaia monoclonal antibody impacts the survival and physiology of adult Anopheles stephensi mosquitoes. Our findings offer useful insight on the role of Asaia in several physiological systems of adult mosquitoes, where the influence differs between males and females.

ACS Style

Maria Vittoria Mancini; Claudia Damiani; Sarah M. Short; Alessia Cappelli; Ulisse Ulissi; Aida Capone; Aurelio Serrao; Paolo Rossi; Augusto Amici; Cristina Kalogris; George Dimopoulos; Irene Ricci; Guido Favia. Inhibition of Asaia in Adult Mosquitoes Causes Male-Specific Mortality and Diverse Transcriptome Changes. Pathogens 2020, 9, 380 .

AMA Style

Maria Vittoria Mancini, Claudia Damiani, Sarah M. Short, Alessia Cappelli, Ulisse Ulissi, Aida Capone, Aurelio Serrao, Paolo Rossi, Augusto Amici, Cristina Kalogris, George Dimopoulos, Irene Ricci, Guido Favia. Inhibition of Asaia in Adult Mosquitoes Causes Male-Specific Mortality and Diverse Transcriptome Changes. Pathogens. 2020; 9 (5):380.

Chicago/Turabian Style

Maria Vittoria Mancini; Claudia Damiani; Sarah M. Short; Alessia Cappelli; Ulisse Ulissi; Aida Capone; Aurelio Serrao; Paolo Rossi; Augusto Amici; Cristina Kalogris; George Dimopoulos; Irene Ricci; Guido Favia. 2020. "Inhibition of Asaia in Adult Mosquitoes Causes Male-Specific Mortality and Diverse Transcriptome Changes." Pathogens 9, no. 5: 380.

Research article
Published: 13 May 2020 in Science Advances
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The malaria parasite’s complex journey through the Anopheles mosquito vector provides multiple opportunities for targeting Plasmodium with recombinant effectors at different developmental stages and different host tissues. We have designed and expressed transgenes that efficiently suppress Plasmodium infection by targeting the parasite with multiple independent endogenous and exogenous effectors at multiple infection stages to potentiate suppression and minimize the probability for development of resistance to develop. We have also addressed the fitness impact of transgene expression on the mosquito. We show that highly potent suppression can be achieved by targeting both pre-oocyst stages by transgenically overexpressing either the endogenous immune deficiency immune pathway transcription factor Rel2 or a polycistronic mRNA encoding multiple antiparasitic effectors and simultaneously targeting the sporozoite stages with an anti-sporozoite single-chain antibody fused to the antiparasitic protein Scorpine. Expression of the selected endogenous effector systems appears to pose a lower fitness cost than does the use of foreign genes.

ACS Style

Yuemei Dong; Maria L. Simões; George Dimopoulos. Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles. Science Advances 2020, 6, eaay5898 .

AMA Style

Yuemei Dong, Maria L. Simões, George Dimopoulos. Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles. Science Advances. 2020; 6 (20):eaay5898.

Chicago/Turabian Style

Yuemei Dong; Maria L. Simões; George Dimopoulos. 2020. "Versatile transgenic multistage effector-gene combinations for Plasmodium falciparum suppression in Anopheles." Science Advances 6, no. 20: eaay5898.

Preprint content
Published: 29 April 2020
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BackgroundSurveillance of mosquito infection status is critical for planning and deployment of proper mosquito control initiatives. Concurrently, Wolbachia is being widely used as a control method for arboviral transmission. Point-of-care (POC) detection assays are necessary for monitoring the infection prevalence and geographic range of viruses as well as Wolbachia in mosquito vector populations. We therefore assessed the novel qPCR bCUBE molecular diagnostic system as a tool for virus and Wolbachia detection.ResultsWe developed a reliable, specific, and sensitive diagnostic assay for detecting Zika virus and dengue virus serotype 2 using the real-time qPCR platform bCUBE. With bCUBE-based qRT-PCR, both Wolbachia bacterium and virus RNA could be reliably detected in individually infected Ae. aegypti mosquitoes and in pools of 5, 10, or 15 mosquitoes.ConclusionsThe portable qPCR bCUBE diagnostic platform is capable of detecting Zika and dengue virus as well as Wolbachia in mosquitoes and therefore has potential as a practical field-deployable diagnostic test for vector-borne disease surveillance programs.

ACS Style

Natalie N. Rutkowski; Yuemei Dong; George Dimopoulos. Field-deployable molecular diagnostic platform for arbovirus and Wolbachia detection in Aedes aegypti. 2020, 1 .

AMA Style

Natalie N. Rutkowski, Yuemei Dong, George Dimopoulos. Field-deployable molecular diagnostic platform for arbovirus and Wolbachia detection in Aedes aegypti. . 2020; ():1.

Chicago/Turabian Style

Natalie N. Rutkowski; Yuemei Dong; George Dimopoulos. 2020. "Field-deployable molecular diagnostic platform for arbovirus and Wolbachia detection in Aedes aegypti." , no. : 1.

Research article
Published: 27 April 2020 in PLOS Genetics
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MicroRNAs (miRNAs) are increasingly recognized as important regulators of many biological processes in mosquitoes, vectors of numerous devastating infectious diseases. Identification of bona fide targets remains the bottleneck for functional studies of miRNAs. In this study, we used CLEAR-CLIP assays to systematically analyze miRNA-mRNA interactions in adult female Anopheles gambiae mosquitoes. Thousands of miRNA-target pairs were captured after direct ligation of the miRNA and its cognate target transcript in endogenous Argonaute–miRNA–mRNA complexes. Using two interactions detected in this manner, miR-309-SIX4 and let-7-kr-h1, we demonstrated the reliability of this experimental approach in identifying in vivo gene regulation by miRNAs. The miRNA-mRNA interaction dataset provided an invaluable opportunity to decipher targeting rules of mosquito miRNAs. Enriched motifs in the diverse targets of each miRNA indicated that the majority of mosquito miRNAs rely on seed-based canonical target recognition, while noncanonical miRNA binding sites are widespread and often contain motifs complementary to the central or 3’ ends of miRNAs. The time-lapse study of miRNA-target interactomes in adult female mosquitoes revealed dynamic miRNA regulation of gene expression in response to varying nutritional sources and physiological demands. Interestingly, some miRNAs exhibited flexibility to use distinct sequences at different stages for target recognition. Furthermore, many miRNA-mRNA interactions displayed stage-specific patterns, especially for those genes involved in metabolism, suggesting that miRNAs play critical roles in precise control of gene expression to cope with enormous physiological demands associated with egg production. The global mapping of miRNA-target interactions contributes to our understanding of miRNA targeting specificity in non-model organisms. It also provides a roadmap for additional studies focused on regulatory functions of miRNAs in Anopheles gambiae.

ACS Style

Xiaonan Fu; Pengcheng Liu; George Dimopoulos; Jinsong Zhu. Dynamic miRNA-mRNA interactions coordinate gene expression in adult Anopheles gambiae. PLOS Genetics 2020, 16, e1008765 .

AMA Style

Xiaonan Fu, Pengcheng Liu, George Dimopoulos, Jinsong Zhu. Dynamic miRNA-mRNA interactions coordinate gene expression in adult Anopheles gambiae. PLOS Genetics. 2020; 16 (4):e1008765.

Chicago/Turabian Style

Xiaonan Fu; Pengcheng Liu; George Dimopoulos; Jinsong Zhu. 2020. "Dynamic miRNA-mRNA interactions coordinate gene expression in adult Anopheles gambiae." PLOS Genetics 16, no. 4: e1008765.

Research article
Published: 24 April 2020 in PLOS Pathogens
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Malaria, caused by the protozoan parasite Plasmodium and transmitted by Anopheles mosquitoes, represents a major threat to human health. Plasmodium’s infection cycle in the Anopheles vector is critical for transmission of the parasite between humans. The midgut-stage bottleneck of infection is largely imposed by the mosquito’s innate immune system. microRNAs (miRNAs, small noncoding RNAs that bind to target RNAs to regulate gene expression) are also involved in regulating immunity and the anti-Plasmodium defense in mosquitoes. Here, we characterized the mosquito’s miRNA responses to Plasmodium infection using an improved crosslinking and immunoprecipitation (CLIP) method, termed covalent ligation of endogenous Argonaute-bound RNAs (CLEAR)-CLIP. Three candidate miRNAs’ influence on P. falciparum infection and midgut microbiota was studied through transgenically expressed miRNA sponges (miR-SPs) in midgut and fat body tissues. MiR-SPs mediated conditional depletion of aga-miR-14 or aga-miR-305, but not aga-miR-8, increased mosquito resistance to both P. falciparum and P. berghei infection, and enhanced the mosquitoes’ antibacterial defenses. Transcriptome analysis revealed that depletion of aga-miR-14 or aga-miR-305 resulted in an increased expression of multiple immunity-related and anti-Plasmodium genes in mosquito midguts. The overall fitness cost of conditionally expressed miR-SPs was low, with only one of eight fitness parameters being adversely affected. Taken together, our results demonstrate that targeting mosquito miRNA by conditional expression of miR-SPs may have potential for the development of malaria control through genetically engineered mosquitoes.

ACS Style

Shengzhang Dong; Xiaonan Fu; Yuemei Dong; Maria L. Simões; Jinsong Zhu; George Dimopoulos. Broad spectrum immunomodulatory effects of Anopheles gambiae microRNAs and their use for transgenic suppression of Plasmodium. PLOS Pathogens 2020, 16, e1008453 .

AMA Style

Shengzhang Dong, Xiaonan Fu, Yuemei Dong, Maria L. Simões, Jinsong Zhu, George Dimopoulos. Broad spectrum immunomodulatory effects of Anopheles gambiae microRNAs and their use for transgenic suppression of Plasmodium. PLOS Pathogens. 2020; 16 (4):e1008453.

Chicago/Turabian Style

Shengzhang Dong; Xiaonan Fu; Yuemei Dong; Maria L. Simões; Jinsong Zhu; George Dimopoulos. 2020. "Broad spectrum immunomodulatory effects of Anopheles gambiae microRNAs and their use for transgenic suppression of Plasmodium." PLOS Pathogens 16, no. 4: e1008453.

Journal article
Published: 27 March 2020
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ACS Style

Eric P Caragata; Luisa M Otero; Jenny S Carlson; Nahid Borhani Dizaji; George Dimopoulos. A non-live preparation of Chromobacterium sp. Panama (Csp_P) is a highly effective larval mosquito biopesticide. 2020, 1 .

AMA Style

Eric P Caragata, Luisa M Otero, Jenny S Carlson, Nahid Borhani Dizaji, George Dimopoulos. A non-live preparation of Chromobacterium sp. Panama (Csp_P) is a highly effective larval mosquito biopesticide. . 2020; ():1.

Chicago/Turabian Style

Eric P Caragata; Luisa M Otero; Jenny S Carlson; Nahid Borhani Dizaji; George Dimopoulos. 2020. "A non-live preparation of Chromobacterium sp. Panama (Csp_P) is a highly effective larval mosquito biopesticide." , no. : 1.

Journal article
Published: 27 March 2020 in Applied and Environmental Microbiology
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Given the continued high prevalence of mosquito-transmitted diseases, there is a clear need to develop novel disease and vector control strategies. Biopesticides of microbial origin represent a promising source of new approaches to target disease-transmitting mosquito populations. Here, we describe the development and characterization of a novel mosquito biopesticide, derived from an air-dried, nonlive preparation of the bacterium Chromobacterium sp. Panama (family: Neisseriaceae). This preparation rapidly and effectively kills the larvae of prominent mosquito vectors, including the dengue and Zika vector Aedes aegypti and the human malaria vector Anopheles gambiae. During semi-field trials in Puerto Rico, we observed high efficacy of the biopesticide against field-derived A. aegypti populations, and against A. aegypti and Culex species larvae in natural breeding water, indicating the suitability of the biopesticide for use under more natural conditions. In addition to high efficacy, the nonlive Csp_P biopesticide has a low effective dose, a long shelf life, and high heat stability and can be incorporated into attractive larval baits, all of which are desirable characteristics for a biopesticide. IMPORTANCE We have developed a novel preparation to kill mosquitoes from an abundant soil bacterium, Chromobacterium sp. Panama. This preparation is an air-dried powder containing no live bacteria, and it can be incorporated into an attractive bait and fed directly to mosquito larvae. We demonstrate that the preparation has broad spectrum activity against the larval form of the mosquitoes responsible for the transmission of malaria and the dengue, chikungunya, yellow fever, West Nile, and Zika viruses, as well as mosquito larvae that are already resistant to commonly used mosquitocidal chemicals. Our preparation possesses many favorable traits: it kills at a low dosage, and it does not lose activity when exposed to high temperatures, all of which suggest that this preparation could eventually become an effective new tool for controlling mosquitoes and the diseases they spread.

ACS Style

Eric P. Caragata; Luisa M. Otero; Jenny S. Carlson; Nahid Borhani Dizaji; George Dimopoulos. A Nonlive Preparation of Chromobacterium sp. Panama (Csp_P) Is a Highly Effective Larval Mosquito Biopesticide. Applied and Environmental Microbiology 2020, 86, 1 .

AMA Style

Eric P. Caragata, Luisa M. Otero, Jenny S. Carlson, Nahid Borhani Dizaji, George Dimopoulos. A Nonlive Preparation of Chromobacterium sp. Panama (Csp_P) Is a Highly Effective Larval Mosquito Biopesticide. Applied and Environmental Microbiology. 2020; 86 (11):1.

Chicago/Turabian Style

Eric P. Caragata; Luisa M. Otero; Jenny S. Carlson; Nahid Borhani Dizaji; George Dimopoulos. 2020. "A Nonlive Preparation of Chromobacterium sp. Panama (Csp_P) Is a Highly Effective Larval Mosquito Biopesticide." Applied and Environmental Microbiology 86, no. 11: 1.

Preprint
Published: 15 October 2019
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A minimum of two blood meals are required for a mosquito to acquire and transmit malaria, yet Anopheles mosquitoes frequently obtain additional blood meals during their adult lifespan. To determine the impact of subsequent blood-feeding on parasite development in Anopheles gambiae, we examined rodent and human Plasmodium parasite infection with or without an additional non-infected blood meal. We find that an additional blood meal significantly reduces P. berghei immature oocyst numbers, yet does not influence mature oocysts that have already begun sporogony. This is in contrast to experiments performed with the human parasite, P. falciparum, where an additional blood meal does not affect oocyst numbers. These observations are reproduced when mosquitoes were similarly challenged with an artificial protein meal, suggesting that parasite losses are due to the physical distension of the mosquito midgut. We provide evidence that feeding compromises the integrity of the midgut basal lamina, enabling the recognition and lysis of immature P. berghei oocysts by the mosquito complement system. Moreover, we demonstrate that additional feeding promotes P. falciparum oocyst growth, suggesting that human malaria parasites exploit host resources provided with blood-feeding to accelerate their growth. This contrasts experiments with P. berghei, where the size of surviving oocysts is independent of an additional blood meal. Together, these data demonstrate differences in the ability of Plasmodium species to evade immune detection and adapt to utilize host resources at the oocyst stage, representing an additional, yet unexplored component of vectorial capacity that has important implications for transmission of malaria.

ACS Style

Hyeogsun Kwon; Rebekah A. Reynolds; Maria Luisa Simoes; George Dimopoulos; Ryan C. Smith. Malaria parasite immune evasion and adaptation to its mosquito host is influenced by the acquisition of multiple blood meals. 2019, 801480 .

AMA Style

Hyeogsun Kwon, Rebekah A. Reynolds, Maria Luisa Simoes, George Dimopoulos, Ryan C. Smith. Malaria parasite immune evasion and adaptation to its mosquito host is influenced by the acquisition of multiple blood meals. . 2019; ():801480.

Chicago/Turabian Style

Hyeogsun Kwon; Rebekah A. Reynolds; Maria Luisa Simoes; George Dimopoulos; Ryan C. Smith. 2019. "Malaria parasite immune evasion and adaptation to its mosquito host is influenced by the acquisition of multiple blood meals." , no. : 801480.

Review article
Published: 23 September 2019 in Natural Product Reports
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In this review, we discuss the merits of using bacterial metabolites – including those secreted by the mosquito microbiota – to combat malaria and filariasis, as well as dengue fever and other arboviral diseases.

ACS Style

Raúl G. Saraiva; George Dimopoulos. Bacterial natural products in the fight against mosquito-transmitted tropical diseases. Natural Product Reports 2019, 37, 338 -354.

AMA Style

Raúl G. Saraiva, George Dimopoulos. Bacterial natural products in the fight against mosquito-transmitted tropical diseases. Natural Product Reports. 2019; 37 (3):338-354.

Chicago/Turabian Style

Raúl G. Saraiva; George Dimopoulos. 2019. "Bacterial natural products in the fight against mosquito-transmitted tropical diseases." Natural Product Reports 37, no. 3: 338-354.

Journal article
Published: 01 September 2019 in Trends in Parasitology
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Traditional control strategies are failing to contain Aedes albopictus as an emerging major vector for dengue. A combination of approaches (Zheng et al., Nature, 2019) involving an artificial triple Wolbachia superinfection and low-dose irradiation enabled mass production of adult sterile males for release. The resulting suppression of field populations suggests feasibility for area-wide vector control.

ACS Style

George Dimopoulos. Combining Sterile and Incompatible Insect Techniques for Aedes albopictus Suppression. Trends in Parasitology 2019, 35, 671 -673.

AMA Style

George Dimopoulos. Combining Sterile and Incompatible Insect Techniques for Aedes albopictus Suppression. Trends in Parasitology. 2019; 35 (9):671-673.

Chicago/Turabian Style

George Dimopoulos. 2019. "Combining Sterile and Incompatible Insect Techniques for Aedes albopictus Suppression." Trends in Parasitology 35, no. 9: 671-673.