Unraveling the Plasmodium vivax sporozoite transcriptional journey from mosquito vector to human host
Ontology highlight
ABSTRACT:
ORGANISM(S): Plasmodium vivax Anopheles dirus
PROVIDER: GSE117538 | GEO | 2018/08/16
REPOSITORIES: GEO
Similar Datasets
Project description:MalariaM-bM-^@M-^Ys cycle of infection requires parasite transmission between a mosquito vector and a vertebrate host. Plasmodium regulates transmission by translationally repressing specific mRNAs until their products are needed. We demonstrate that the Plasmodium yoelii Pumilio-FBF family member Puf2 allows the sporozoite to retain its infectivity in the mosquito salivary glands while awaiting transmission. Puf2 mediates this critical feature solely through its RNA-Binding Domain (RBD) likely by protecting and silencing specific mRNAs. Puf2 storage granules are distinct from stress granules and P-bodies and dissolve rapidly after infection of hepatocytes, likely releasing the protected and silenced transcripts for M-bM-^@M-^Xjust-in-timeM-bM-^@M-^Y translation by early exoerythrocytic forms (EEFs). Further corroborating this model, pypuf2- sporozoites have no apparent defect in host infection early after invading the salivary glands, but become progressively noninfectious and subsequently prematurely transform into EEFs during prolonged salivary gland residence. In contrast, the premature overexpression of Puf2 in oocysts causes striking deregulation of sporozoite maturation, resulting in fewer oocyst sporozoites that are non-infectious and unable to colonize the salivary glands. Maintenance of Puf2 expression in liver stage parasites produces no phenotype, suggesting that a window of permissive expression exists. Finally, by conducting the first comparative RNAseq analysis of Plasmodium sporozoites, we have uncovered that Puf2 may play a role in both the protection of specific transcripts as well as RNA turnover via the CCR4/Not complex. These findings uncover requirements for maintaining a window of opportunity for the malaria parasite to accommodate the unpredictable moment of transmission from mosquito to vertebrate host. Wild-type (Py17XNL) and pypuf2 -salivary gland sporozoites
2012-10-27 | E-GEOD-41873 | biostudies-arrayexpress
Project description:Malaria’s cycle of infection requires parasite transmission between a mosquito vector and a vertebrate host. Plasmodium regulates transmission by translationally repressing specific mRNAs until their products are needed. We demonstrate that the Plasmodium yoelii Pumilio-FBF family member Puf2 allows the sporozoite to retain its infectivity in the mosquito salivary glands while awaiting transmission. Puf2 mediates this critical feature solely through its RNA-Binding Domain (RBD) likely by protecting and silencing specific mRNAs. Puf2 storage granules are distinct from stress granules and P-bodies and dissolve rapidly after infection of hepatocytes, likely releasing the protected and silenced transcripts for ‘just-in-time’ translation by early exoerythrocytic forms (EEFs). Further corroborating this model, pypuf2- sporozoites have no apparent defect in host infection early after invading the salivary glands, but become progressively noninfectious and subsequently prematurely transform into EEFs during prolonged salivary gland residence. In contrast, the premature overexpression of Puf2 in oocysts causes striking deregulation of sporozoite maturation, resulting in fewer oocyst sporozoites that are non-infectious and unable to colonize the salivary glands. Maintenance of Puf2 expression in liver stage parasites produces no phenotype, suggesting that a window of permissive expression exists. Finally, by conducting the first comparative RNAseq analysis of Plasmodium sporozoites, we have uncovered that Puf2 may play a role in both the protection of specific transcripts as well as RNA turnover via the CCR4/Not complex. These findings uncover requirements for maintaining a window of opportunity for the malaria parasite to accommodate the unpredictable moment of transmission from mosquito to vertebrate host.
2012-10-27 | GSE41873 | GEO
Project description:Sporozoite is the stage in which malaria parasites initially infect the vertebrate host. Elucidation of gene regulation in this stage will promote the investigation of mechanisms of liver infection by this parasite and contribute to development of strategies for preventing the malaria transmission. AP2-Sp is a transcription factor essential for formation of sporozoites or sporogony, which take place in oocysts on the midgut of infected mosquitoes. To understand the role of this transcription factor in the transcriptional regulatory system of this stage we performed ChIP-seq analysis using whole mosquito midguts containing late oocysts as start materials and explore its target genes genome-widely. Target genes were composed of 640 genes, which encompassed various functional categories and were contained genes involved in distinct processes parasites pass through in this stage, from sporogony to development into the liver stage. Furthermore, RNA-seq analysis showed that these genes constituted majority of the genes highly expressed in in this stage. These results suggested that this TF determines basal pattern of gene expression of this stage by targeting a broad range of genes directly.
2022-11-05 | GSE212753 | GEO
Project description:Sporozoite is the stage in which malaria parasites initially infect the vertebrate host. Elucidation of gene regulation in this stage will promote the investigation of mechanisms of liver infection by this parasite and contribute to development of strategies for preventing the malaria transmission. AP2-Sp is a transcription factor essential for formation of sporozoites or sporogony, which take place in oocysts on the midgut of infected mosquitoes. To understand the role of this transcription factor in the transcriptional regulatory system of this stage we performed ChIP-seq analysis using whole mosquito midguts containing late oocysts as start materials and explore its target genes genome-widely. Target genes were composed of 640 genes, which encompassed various functional categories and were contained genes involved in distinct processes parasites pass through in this stage, from sporogony to development into the liver stage. Furthermore, RNA-seq analysis showed that these genes constituted majority of the genes highly expressed in in this stage. These results suggested that this TF determines basal pattern of gene expression of this stage by targeting a broad range of genes directly.
2022-11-05 | GSE188985 | GEO
Project description:This is a coupled multiscale mathematical model of malaria control and elimination containing four submodels: mosquito-to-human transmission of the malaria parasite, human-to-mosquito transmission of the malaria parasite, a within-mosquito malaria parasite population dynamics sub-model and a within-human malaria parasite population dynamics sub-model.
Model is encoded by Johannes and submitted to BioModels by Ahmad Zyoud.
2020-03-20 | MODEL2003190008 | BioModels
Project description:Background: The mosquito Anopheles gambiae is a major vector of human malaria. Increasing evidence indicates that blood cells (hemocytes) comprise an essential arm of the mosquito innate immune response against both bacteria and malaria parasites. To further characterize the role of hemocytes in mosquito immunity, we undertook the first genome-wide transcriptomic analyses of adult female An. gambiae hemocytes following infection by two species of bacteria and a malaria parasite. Results: We identified 4047 genes expressed in hemocytes, using An. gambiae genome-wide microarrays. While 279 transcripts were significantly enriched in hemocytes relative to whole adult female mosquitoes, 959 transcripts exhibited immune challenge-related regulation. The global transcriptomic responses of hemocytes to challenge with different species of bacteria and/or different stages of malaria parasite infection revealed discrete, minimally overlapping, pathogen-specific signatures of infection-responsive gene expression; 105 of these represented putative immunity-related genes including anti-Plasmodium factors. Of particular interest was the specific co-regulation of various members of the Imd and JNK immune signaling pathways during malaria parasite invasion of the mosquito midgut epithelium. Conclusion: Our genome-wide transcriptomic analysis of adult mosquito hemocytes reveals pathogen-specific signatures of gene regulation and identifies several novel candidate genes for future functional studies. In order to identify hemocyte-specific and immune-responsive transcripts, we first compared transcripts expressed in hemocytes from one day old sugar-fed mosquitoes to transcripts detected in whole mosquitoes of the same age and feeding status. This resulted in identification of the hemocyte-enriched transcriptome. We then compared hemocytes from 1 day old mosquitoes, 1 hour after immune challenge with heat-killed Escherichia coli or Micrococcus luteus, to control female mosquitoes injected with sterile PBS to determine the bacteria challenge responsive transcriptomes. We used heat-killed bacteria in these assays, because our primary interest was in identifying the bacterial responsive transcriptome and to avoid the potentially confounding effects of altered gene expression due to the lethal effects of a systemic infection associated with injection of living bacteria. Lastly, we compared hemocytes from mosquitoes at 24 hours and 19 days after ingestion of a blood meal infected with Plasmodium berghei to mosquitoes of the same age fed a non-infected blood meal to determine the ookinete and sporozoite infection responsive transcriptomes, respectively. This design resulted in a total of five experimental treatments. The following samples are not included in this submission: Hemo E coli vs. hemo unchallenged A Hemo E coli vs. hemo unchallenged B Hemo m luteus vs. hemo unchallenged A Hemo m luteus vs. hemo unchallenged B
2011-10-31 | E-GEOD-33269 | biostudies-arrayexpress
Project description:Background: The mosquito Anopheles gambiae is a major vector of human malaria. Increasing evidence indicates that blood cells (hemocytes) comprise an essential arm of the mosquito innate immune response against both bacteria and malaria parasites. To further characterize the role of hemocytes in mosquito immunity, we undertook the first genome-wide transcriptomic analyses of adult female An. gambiae hemocytes following infection by two species of bacteria and a malaria parasite. Results: We identified 4047 genes expressed in hemocytes, using An. gambiae genome-wide microarrays. While 279 transcripts were significantly enriched in hemocytes relative to whole adult female mosquitoes, 959 transcripts exhibited immune challenge-related regulation. The global transcriptomic responses of hemocytes to challenge with different species of bacteria and/or different stages of malaria parasite infection revealed discrete, minimally overlapping, pathogen-specific signatures of infection-responsive gene expression; 105 of these represented putative immunity-related genes including anti-Plasmodium factors. Of particular interest was the specific co-regulation of various members of the Imd and JNK immune signaling pathways during malaria parasite invasion of the mosquito midgut epithelium. Conclusion: Our genome-wide transcriptomic analysis of adult mosquito hemocytes reveals pathogen-specific signatures of gene regulation and identifies several novel candidate genes for future functional studies.
2011-10-31 | GSE33269 | GEO
Project description:Many eukaryotic developmental and cell fate decisions are effected post-transcriptionally that mechanistically involve RNA binding proteins as regulators of translation of key mRNAs. In the unicellular eukaryote malaria parasite, Plasmodium, one of the most dramatic changes in cell morphology and function occurs during transmission between mosquito and human host. In the mosquito salivary glands, Plasmodium sporozoites are slender, motile and remain infectious for several weeks; only after transmission and liver cell invasion, does the parasite rapidly transform into a round, non-motile exo-erythrocytic form (EEF) that gives rise to thousands of infectious merozoites to be released into the blood stream. Here we demonstrate a Plasmodium homolog of the RNA binding protein, Pumilio, as a key regulator of the sporozoite to EEF transformation. In the absence of Pumilio-2 (Puf2) Plasmodium berghei sporozoites initiate early stage EEF development inside mosquito salivary glands with characteristic morphological changes; puf2- salivary gland sporozoites lose gliding motility, cell traversal ability and are less infective. Global expression profiling confirmed that transgenic parasites exhibit genome-wide transcriptional adaptations typical for Plasmodium intra-hepatic development. The data demonstrate that Puf2 is a key player in regulating developmental control, and imply that transformation of salivary gland-resident sporozoites into early liver stage parasites is regulated by a post-translational mechanism.
2010-11-01 | E-TABM-1067 | biostudies-arrayexpress
Project description:Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years, and then reactivate to cause recurrent blood-stage infection. While an important target for malaria eradication, little is known about the molecular features of the replicative and non-replicative states of intracellular P. vivax parasites, or their human host-cell dependencies and the host responses to them. Here, we leverage a bioengineered human microliver platform to culture patient-derived P. vivax parasites in primary human hepatocytes and conduct transcriptional profiling. By coupling enrichment strategies with bulk and single-cell analyses, we captured both parasite and host transcripts in individual hepatocytes throughout the infection course. We define host- and state-dependent transcriptional signatures and identify previously unappreciated populations of replicative and non-replicative parasites, sharing features with sexual transmissive forms. We find that infection suppresses transcription of key hepatocyte function genes, and that P. vivax elicits an innate immune response that can be manipulated to control infection. Our work provides an extendible framework and resource for understanding host-parasite interactions and reveals new insights into the biology of P. vivax dormancy and transmission.
2022-02-25 | GSE197409 | GEO
Project description:Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years, and then reactivate to cause recurrent blood-stage infection. While an important target for malaria eradication, little is known about the molecular features of the replicative and non-replicative states of intracellular P. vivax parasites, or their human host-cell dependencies and the host responses to them. Here, we leverage a bioengineered human microliver platform to culture patient-derived P. vivax parasites in primary human hepatocytes and conduct transcriptional profiling. By coupling enrichment strategies with bulk and single-cell analyses, we captured both parasite and host transcripts in individual hepatocytes throughout the infection course. We define host- and state-dependent transcriptional signatures and identify previously unappreciated populations of replicative and non-replicative parasites, sharing features with sexual transmissive forms. We find that infection suppresses transcription of key hepatocyte function genes, and that P. vivax elicits an innate immune response that can be manipulated to control infection. Our work provides an extendible framework and resource for understanding host-parasite interactions and reveals new insights into the biology of P. vivax dormancy and transmission.
2022-02-25 | GSE197458 | GEO