scholarly journals The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum

PLoS Biology ◽  
2003 ◽  
Vol 1 (1) ◽  
pp. e5 ◽  
Author(s):  
Zbynek Bozdech ◽  
Manuel Llinás ◽  
Brian Lee Pulliam ◽  
Edith D Wong ◽  
Jingchun Zhu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Developmental Cycle ◽  
Intraerythrocytic Developmental Cycle

scholarly journals Refining the transcriptome of the human malaria parasite Plasmodium falciparum using amplification-free RNA-seq

2019 ◽  
Author(s):  
Lia Chappell ◽  
Philipp Ross ◽  
Lindsey Orchard ◽  
Thomas D. Otto ◽  
Matthew Berriman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Developmental Cycle ◽  
Rna Seq ◽  
Human Malaria Parasite ◽  
Human Malaria ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Intraerythrocytic Developmental Cycle ◽  
Transcriptional Start Sites

AbstractPlasmodium parasites undergo several major developmental transitions during their complex lifecycle, which are enabled by precisely ordered gene expression programs. Transcriptomes from the 48-hour blood stages of the major human malaria parasite Plasmodium falciparum have been described using cDNA microarrays and RNA-seq, but these assays have not always performed well within non-coding regions, where the AT-content is often 90-95%. We developed a directional, amplification-free RNA-seq protocol (DAFT-seq) to reduce bias against AT-rich cDNA, which we have applied to three strains of P. falciparum (3D7, HB3 and IT). While strain-specific differences were detected, overall there is strong conservation between the transcriptional profiles. For the 3D7 reference strain, transcription was detected from 89% of the genome, with over 75% of the genome transcribed into mRNAs. These datasets allowed us to refine the 5’ and 3’ untranslated regions (UTRs), which can be variable, long (>1,000 nt), and often overlap those of adjacent transcripts. We also find that transcription from bidirectional promoters frequently results in non-coding, antisense transcripts. By capturing the 5’ ends of mRNAs, we reveal both constant and dynamic use of transcriptional start sites across the intraerythrocytic developmental cycle resulting in an updated view of the P. falciparum transcriptome.

scholarly journals Biosynthesis of GDP-fucose and Other Sugar Nucleotides in the Blood Stages of Plasmodium falciparum

2013 ◽  
Vol 288 (23) ◽  
pp. 16506-16517 ◽  
Author(s):  
Sílvia Sanz ◽  
Giulia Bandini ◽  
Diego Ospina ◽  
Maria Bernabeu ◽  
Karina Mariño ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
De Novo ◽  
Cell Communication ◽  
Developmental Cycle ◽  
Metabolic Labeling ◽  
Sugar Nucleotides ◽  
Liquid Chromatography Tandem Mass ◽  
Intraerythrocytic Developmental Cycle

Carbohydrate structures play important roles in many biological processes, including cell adhesion, cell-cell communication, and host-pathogen interactions. Sugar nucleotides are activated forms of sugars used by the cell as donors for most glycosylation reactions. Using a liquid chromatography-tandem mass spectrometry-based method, we identified and quantified the pools of UDP-glucose, UDP-galactose, UDP-N-acetylglucosamine, GDP-mannose, and GDP-fucose in Plasmodium falciparum intraerythrocytic life stages. We assembled these data with the in silico functional reconstruction of the parasite metabolic pathways obtained from the P. falciparum annotated genome, exposing new active biosynthetic routes crucial for further glycosylation reactions. Fucose is a sugar present in glycoconjugates often associated with recognition and adhesion events. Thus, the GDP-fucose precursor is essential in a wide variety of organisms. P. falciparum presents homologues of GDP-mannose 4,6-dehydratase and GDP-l-fucose synthase enzymes that are active in vitro, indicating that most GDP-fucose is formed by a de novo pathway that involves the bioconversion of GDP-mannose. Homologues for enzymes involved in a fucose salvage pathway are apparently absent in the P. falciparum genome. This is in agreement with in vivo metabolic labeling experiments showing that fucose is not significantly incorporated by the parasite. Fluorescence microscopy of epitope-tagged versions of P. falciparum GDP-mannose 4,6-dehydratase and GDP-l-fucose synthase expressed in transgenic 3D7 parasites shows that these enzymes localize in the cytoplasm of P. falciparum during the intraerythrocytic developmental cycle. Although the function of fucose in the parasite is not known, the presence of GDP-fucose suggests that the metabolite may be used for further fucosylation reactions.

A new Plasmodium falciparum field isolate from Benin in continuous culture: Infectivity of fresh-produced and cryopreserved gametocytes to Anopheles gambiae

2021 ◽  
Author(s):  
Adandé A. Medjigbodo ◽  
Festus K. Acquah ◽  
Laurette Djossou ◽  
Linda E. Amoah ◽  
Edgard-Marius Ouendo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Anopheles Gambiae ◽  
Field Isolate ◽  
Infected Mosquito ◽  
Developmental Cycle ◽  
Transmission Blocking ◽  
Field Isolates ◽  
Replication Studies ◽  
Intraerythrocytic Developmental Cycle ◽  
Transmission Blocking Vaccines

Abstract Transmission-blocking vaccines and drugs are likely to be key interventions in efforts to achieve malaria elimination. However, transmission-blocking studies are reliant upon a limited number of culture-adapted strains of Plasmodium falciparum with limited genetic variability, or on field isolates which are only maintained transiently in the laboratory and therefore not amenable to replication studies. Herein, we investigated the gametocytogenesis capacity and infectivity to Anopheles gambiae mosquitoes of a P. falciparum field isolate collected from a malaria patient from Benin compared to those of NF54 strain. The intraerythrocytic developmental cycle (IDC) was similar in both P. falciparum strains (ranges of parasitaemias were respectively 0.02–11.53% and 0.035–10.5% throughout twelve days of culture). The culture-adapted parasites displayed a significant higher infectivity to An. gambiae compared to that of NF54 (mean oocyst prevalence and intensity: 16.94%, CI95%= [15.15–18.73] vs. 3.13%, CI95%= [2.30–3.96], p < 0.0001 and 3 vs. 1 oocysts/infected mosquito, p = 0.002 respectively). Even after cryopreservation for up to 14 days, gametocytes from the field isolates were capable of infecting An. gambiae mosquitoes at a prevalence of up to 30% with an average of 12 oocysts/ midgut. This new P. falciparum strain will enhance malaria transmission-blocking studies in endemic countries.

scholarly journals Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Richard Thomson-Luque ◽  
Lasse Votborg-Novél ◽  
Wanangwa Ndovie ◽  
Carolina M. Andrade ◽  
Moussa Niangaly ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Disease Severity ◽  
Parasite Burden ◽  
Clinical Severity ◽  
Circulation Time ◽  
Developmental Cycle ◽  
Clinical Presentations ◽  
Transcriptional Pattern ◽  
Bioinformatic Approaches ◽  
Intraerythrocytic Developmental Cycle

AbstractFollowing Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum’s tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity.

scholarly journals Real-time in vivo Global Transcriptional Dynamics During Plasmodium falciparum Blood-stage Development

2018 ◽  
Author(s):  
Heather J. Painter ◽  
Neo Christopher Chung ◽  
Aswathy Sebastian ◽  
Istvan Albert ◽  
John D. Storey ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Global Analysis ◽  
Mrna Abundance ◽  
Developmental Cycle ◽  
Sequence Motifs ◽  
Erythrocyte Invasion ◽  
Pyrimidine Salvage ◽  
Active Transcription ◽  
Intraerythrocytic Developmental Cycle

ABSTRACTGenome-wide analysis of transcription in the human malaria parasite Plasmodium falciparum has revealed robust variation in steady-state mRNA abundance throughout the 48-hour intraerythrocytic developmental cycle (IDC) suggesting that this process is highly dynamic and tightly regulated. However, the precise timing of mRNA transcription and decay remains poorly understood due to the utilization of methods that only measure total RNA and cannot differentiate between newly transcribed, decaying and stable cellular RNAs. Here we utilize rapid 4-thiouracil (4-TU) incorporation via pyrimidine salvage to specifically label, capture and quantify newly-synthesized P. falciparum RNA transcripts at every hour throughout the IDC following erythrocyte invasion. This high resolution global analysis of the transcriptome captures the timing and rate of transcription for each newly synthesized mRNA in vivo, revealing active transcription throughout all stages of the IDC. To determine the fraction of active transcription and/or transcript stabilization contributing to the total mRNA abundance at each timepoint we have generated a statistical model to fit the data for each gene which reveals varying degrees of transcription and stabilization for each mRNA corresponding to developmental transitions and independent of abundance profile. Finally, our results provide new insight into co-regulation of mRNAs throughout the IDC through regulatory DNA sequence motifs associated with these processes, thereby expanding our understanding of P. falciparum mRNA dynamics.

Modeling metabolism and stage-specific growth of Plasmodium falciparum HB3 during the intraerythrocytic developmental cycle

2014 ◽  
Vol 10 (10) ◽  
pp. 2526-2537 ◽  
Author(s):  
Xin Fang ◽  
Jaques Reifman ◽  
Anders Wallqvist
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Metabolic Network ◽  
Network Model ◽  
Specific Growth ◽  
Time Dependent ◽  
Developmental Cycle ◽  
Physiological Functions ◽  
Metabolic Network Model ◽  
Intraerythrocytic Developmental Cycle

We developed a metabolic network model that maps hourly gene expression to time-dependent metabolism and stage-specific growth, allowing us to link specific metabolites or pathways to specific physiological functions.

scholarly journals Patterns of Gene-Specific and Total Transcriptional Activity during the Plasmodium falciparum Intraerythrocytic Developmental Cycle

2009 ◽  
Vol 8 (3) ◽  
pp. 327-338 ◽  
Author(s):  
Jennifer S. Sims ◽  
Kevin T. Militello ◽  
Peter A. Sims ◽  
Vishal P. Patel ◽  
Jacob M. Kasper ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Transcriptional Activity ◽  
Regulatory Mechanisms ◽  
Parasite Development ◽  
Developmental Cycle ◽  
Activity Levels ◽  
Time Points ◽  
Sense Strand ◽  
Gene Regulatory ◽  
Intraerythrocytic Developmental Cycle

ABSTRACT The relationships among gene regulatory mechanisms in the malaria parasite Plasmodium falciparum throughout its asexual intraerythrocytic developmental cycle (IDC) remain poorly understood. To investigate the level and nature of transcriptional activity and its role in controlling gene expression during the IDC, we performed nuclear run-on on whole-transcriptome samples from time points throughout the IDC and found a peak in RNA polymerase II-dependent transcriptional activity related to both the number of nuclei per parasite and variable transcriptional activity per nucleus over time. These differential total transcriptional activity levels allowed the calculation of the absolute transcriptional activities of individual genes from gene-specific nuclear run-on hybridization data. For half of the genes analyzed, sense-strand transcriptional activity peaked at the same time point as total activity. The antisense strands of several genes were substantially transcribed. Comparison of the transcriptional activity of the sense strand of each gene to its steady-state RNA abundance across the time points assayed revealed both correlations and discrepancies, implying transcriptional and posttranscriptional regulation, respectively. Our results demonstrate that such comparisons can effectively indicate gene regulatory mechanisms in P. falciparum and suggest that genes with diverse transcriptional activity levels and patterns combine to produce total transcriptional activity levels tied to parasite development during the IDC.

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