Signaling between mammalian adiponectin and a mosquito adiponectin receptor reduces Plasmodium transmission
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ABSTRACT:
PROVIDER: PRJNA817525 | ENA |
REPOSITORIES: ENA
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Project description:In this study we determine the effects of silencing adiponectin receptor in A. gambiae mosquitoes after taking Plasmodium gambiae infected blood meals. dsRNA (dsAdpR and dsGluc) microinjected A. gambiae mosquitoes were fed on P. berghei-infected Swiss Webster mice. Two days after a blood meal, the mosquitoes were collected for midgut dissection.
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Project description:Transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by the intraerythrocytic gametocytes, which, once taken up during a blood meal, become activated to initiate sexual reproduction. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they are crucial for spreading the tropical disease. During gametocyte maturation, different repertoires of genes are switched on and off in a well-coordinated sequence, pointing to regulatory mechanisms of gene expression. While epigenetic gene control has been studied during erythrocytic schizogony of P. falciparum, little is known about this process during parasite human-to-mosquito transmission of the parasite. To unveil the potential role of histone acetylation during gene expression in gametocytes, we carried out a microarray-based transcriptome analysis on gametocytes treated with the histone deacetylase inhibitor trichostatin A (TSA).
2017-05-24 | GSE99223 | GEO
Project description:Mosquitoes transmit many flaviviruses of global public health significance. Efficient viral transmission to mammalian hosts requires mosquito salivary factors that modulate local host responses, such as recruitment of virus-permissive myeloid cells to the bite sites. However, the specific salivary components facilitating viral transmission and their mechanisms of action remain largely unknown. Here, we showed that a female mosquito salivary gland-specific protein, named Aedes aegypti Neutrophil Recruitment Protein (AaNRP), acts as a key salivary component to facilitate the transmission of Zika (ZIKV) and dengue (DENV) viruses. AaNRP promotes a rapid influx of neutrophils followed by virus-susceptible myeloid cells toward mosquito bite sites, which facilitate establishment of local infection and systemic dissemination. Mechanistically, AaNRP engages TLR1 and TLR4 of skin resident macrophages and activates MyD88-dependent NF-κB signaling to induce the expression of neutrophil chemoattractants. Inhibition of MyD88-NF-κB with dietary resveratrol, a phytochemical, neutralizes the AaNRP effects, thus reducing flavivirus transmission by mosquitoes. This study offers mechanistic insight into saliva-aided viral transmission and provides a potential prophylactic target.
2023-05-18 | GSE232756 | GEO
Project description:Mosquito-borne helminth infections are responsible for a significant worldwide disease burden in both humans and animals. Accordingly, development of novel strategies to reduce disease transmission by targeting these pathogens in the vector are of paramount importance. We found that a strain of Aedes aegypti that is refractory to infection by Dirofilaria immitis, the agent of canine heartworm disease, mounts a stronger immune response during infection than does a susceptible strain. Moreover, activation of the Toll immune signaling pathway in the susceptible strain arrests larval development of the parasite, thereby decreasing the number of transmissionstage larvae. Notably, this strategy also blocks transmission stage Brugia malayi, an agent of human lymphatic filariasis. Our data show that mosquito immunity can play a pivotal role in restricting filarial nematode development and suggest that genetically engineering mosquitoes with enhanced immunity will help reduce disease transmission.
2020-02-01 | GSE142155 | GEO
Project description:Transmission of malaria parasites from humans to the mosquito vector exclusively relies on the sexual reproduction of the parasite within the mosquito blood meal. Upon ingestion, Plasmodium male gametocyte undergoes explosive development: within 10 minutes, it completes three rounds of genome replication and endomitosis, assembles eight axonemes, and emerges from the host red blood cell. The plant-like calcium-dependent protein kinase 4 (CDPK4) was previously shown to be essential for male gametogenesis placing this kinase as an attractive drug target to block malaria transmission. Here we have identified and resolved three distinct molecular functions of CDPK4 during male gametogenesis. Activity of a myristoylated isoform is first required up to 20 seconds after activation to load the Mini-Chromosome Maintenance complex onto origins of replication. This role is partially mediated by a conserved protein belonging to the SAPS-domain family which is involved in the G1 to S-phase transition in eukaryotes. At the same time, activity of myristoylated CDPK4 is required to phosphorylate a Plasmodium-specific microtubule-associated protein necessary for mitotic spindle assembly. Finally, activity of a short non-myristoylated isoform of CDPK4 is essential seconds prior to completion of cytokinesis and the activation of male gamete motility. This late role has been linked to another Plasmodium-specific protein that is incorporated into axonemes during gametogenesis. This study reveals how a kinase of a protist parasite integrates and transduces multiple signals with a high spatiotemporal resolution to control both evolutionarily conserved and Plasmodium-specific biological processes.
2017-05-24 | PXD005884 | Pride
Project description:The blood-feeding behavior of Anopheles females delivers essential nutrients for egg development and drives parasite transmission between humans. Plasmodium growth is adapted to the vector reproductive cycle, but how changes in the reproductive cycle impact parasite development remains unclear. Here, we show that the bloodmeal-induced miR-276-5p fine-tunes the expression of branched-chain amino acid transferase to terminate the reproductive cycle. Silencing of miR-276 prolongs high rates of amino acid (AA) catabolism and increases female fertility, suggesting that timely termination of AA catabolism restricts mosquito investment into reproduction. Prolongation of AA catabolism in P. falciparum-infected females also compromises the development of the transmissible sporozoite forms. Our results suggest that Plasmodium sporogony exploits the surplus mosquito resources available after reproductive investment and demonstrate the crucial role of the mosquito AA metabolism in within-vector parasite proliferation and malaria transmission.
2021-11-03 | MTBLS1282 | MetaboLights
Project description:Plasmodium sporozoites are injected, in addition to saliva, into animal hosts when a female Anopheles mosquito takes a blood meal. The molecular components of saliva that interact with Plasmodium during this process are poorly characterized. Here we collected Plasmodium sporozoites directly from salivating Anopheles mosquitoes and looked for the presence of vector proteins that could be interacting with the parasites during transmission for further characterization.
2018-10-18 | PXD010121 | Pride
Project description:Transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is initiated by sexual precursor cells, the gametocytes. Gametocytes are formed in response to stress signals and following up-take by a blood-feeding Anopheles mosquito initiate sexual reproduction. Gametocytes need to fine tune their gene expression in order to develop inside the mosquito to continue life-cycle progression. Previously we showed that post-translational histone acetylation controls gene expression during gametocyte development and transmission. However, the role of histone methylation remains poorly understood. We here use the histone G9a methyltransferase inhibitor BIX-01294 to investigate the role of histone methylation in regulating gene expression in gametocytes. Growth assays demonstrated that BIX-01294 inhibits intraerythrocytic replication with an IC50 of 13.0 nM. Furthermore, BIX-01294 significantly impairs gametocyte maturation and reduces the formation of gametes and zygotes. Comparative transcriptomics between BIX-01294-treated and untreated immature, mature and activated gametocytes demonstrated greater than 1.5-fold deregulation of over 359 genes. The majority of these genes are transcriptionally down-regulated in the activated gametocytes and could be assigned to transcription, translation, and signaling indicating a contribution of histone methylations in mediating gametogenesis. Our combined data shows that inhibitors of histone methylation may serve as a multi-stage antimalarials.
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Project description:Host-derived factors are sucked into midgut of mosquitoes during natural malaria transmission, but their influence on malaria transmission is largely unknown. We reported that mouse complement C3 taken into mosquitoes significantly promoted malaria transmission either in laboratory or in field. This effect was attributed to the reduction of microbiota abundance in mosquito midgut by host-derived C3 through direct lyses the predominant symbiont bacteria Elizabethkingia anopheles. Elizabethkingia anopheles symbiont bacteria were demonstrated to be detrimental to malaria sexual stages in mosquitoes. Strikingly, the promoted effect of host C3 on malaria transmission was confirmed by laboratory mosquitoes membrane-feeding on Plasmodium falciparum. Therefore, we reveal a novel strategy of malaria parasite to utilize host complement C3 to promote its transmission, and the administration of C3 inhibitor would provide us a novel strategy to control malaria transmission.
2024-08-01 | GSE271070 | GEO
Project description:Here we characterize the function of a microneme protein expressed both in merozoites and sporozoites, the claudin-like protein CLAMP. We used a conditional genome editing strategy in a rodent malaria model to generate CLAMP-deficient sporozoites. In the absence of CLAMP, sporozoites failed to invade mosquito salivary glands and mammalian hepatocytes, and showed defects in gliding motility and microneme secretion. Our data establish that CLAMP plays an essential role across Plasmodium invasive stages, and might represent a potential target for transmission-blocking antimalarial strategies.
2023-05-10 | PXD037561 | Pride