scholarly journals An intrinsic oscillator drives the blood stage cycle of the malaria parasite Plasmodium falciparum

Science ◽  
2020 ◽  
Vol 368 (6492) ◽  
pp. 754-759 ◽  
Author(s):  
Lauren M. Smith ◽  
Francis C. Motta ◽  
Garima Chopra ◽  
J. Kathleen Moch ◽  
Robert R. Nerem ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Blood Stage ◽  
Developmental Cycle ◽  
Cycle Period ◽  
Molecular Signatures ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Cell Variance

The blood stage of the infection of the malaria parasite Plasmodium falciparum exhibits a 48-hour developmental cycle that culminates in the synchronous release of parasites from red blood cells, which triggers 48-hour fever cycles in the host. This cycle could be driven extrinsically by host circadian processes or by a parasite-intrinsic oscillator. To distinguish between these hypotheses, we examine the P. falciparum cycle in an in vitro culture system and show that the parasite has molecular signatures associated with circadian and cell cycle oscillators. Each of the four strains examined has a different period, which indicates strain-intrinsic period control. Finally, we demonstrate that parasites have low cell-to-cell variance in cycle period, on par with a circadian oscillator. We conclude that an intrinsic oscillator maintains Plasmodium’s rhythmic life 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 Organoarsenic Compounds with In Vitro Activity against the Malaria Parasite Plasmodium falciparum

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 260
Author(s):  
Sofia Basova ◽  
Nathalie Wilke ◽  
Jan Christoph Koch ◽  
Aram Prokop ◽  
Albrecht Berkessel ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Rapid Development ◽  
Sexual Transmission ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
In Vitro Assays ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

The rapid development of parasite drug resistance as well as the lack of medications targeting both the asexual and the sexual blood stages of the malaria parasite necessitate the search for novel antimalarial compounds. Eleven organoarsenic compounds were synthesized and tested for their effect on the asexual blood stages and sexual transmission stages of the malaria parasite Plasmodium falciparum using in vitro assays. The inhibitory potential of the compounds on blood stage viability was tested on the chloroquine (CQ)-sensitive 3D7 and the CQ-resistant Dd2 strain using the Malstat assay. The most effective compounds were subsequently investigated for their effect on impairing gametocyte development and gametogenesis, using the gametocyte-producing NF54 strain in respective cell-based assays. Their potential toxicity was investigated on leukemia cell line Nalm-6 and non-infected erythrocytes. Five out of the 11 compounds showed antiplasmodial activities against 3D7, with half-maximal inhibitory concentration (IC50) values ranging between 1.52 and 8.64 µM. Three of the compounds also acted against Dd2, with the most active compound As-8 exhibiting an IC50 of 0.35 µM. The five compounds also showed significant inhibitory effects on the parasite sexual stages at both IC50 and IC90 concentrations with As-8 displaying the best gametocytocidal activity. No hemolytic and cytotoxic effect was observed for any of the compounds. The organoarsenic compound As-8 may represent a good lead for the design of novel organoarsenic drugs with combined antimalarial and transmission blocking activities.

scholarly journals Polymorphism of a high molecular weight schizont antigen of the human malaria parasite Plasmodium falciparum.

1985 ◽  
Vol 161 (1) ◽  
pp. 160-180 ◽  
Author(s):  
J S McBride ◽  
C I Newbold ◽  
R Anand
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Peptide Mapping ◽  
Human Malaria Parasite ◽  
Human Malaria ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Immunological Classification ◽  
Specific Antigens

Intraspecies antigenic diversity in the blood stages of the human malaria parasite Plasmodium falciparum was investigated using a collection of murine monoclonal antibodies and clones of the parasite. The results were as follows: (a) The schizont and merozoite stages of the parasite express on their surface clonally restricted antigens detectable by strain-specific antibodies in indirect immunofluorescence tests. (b) These restricted antigens are phenotypically stable characteristics of clones grown in vitro. (c) The molecules carrying the specific antigens were isolated by immunoprecipitation and were found to be parasite proteins ranging in size from Mr 190,000 to 200,000 between clones. (d) Comparative immunoprecipitation and peptide mapping of these molecules showed that each parasite clone expresses a protein that is antigenically and structurally distinct from the equivalent products of several other clones. (e) The different clonal products are, however, immunologically interrelated, since they possess determinants in common with all tested isolates of the parasite. (f) These polymorphic molecules are closely related to a previously described schizont protein of P. falciparum that is posttranslationally cleaved into fragments located on the merozoite surface. These findings show the existence of a family of related polymorphic schizont antigens (PSA) of P. falciparum, whose expression is clonally restricted, and indicate that these proteins have regions of constant and variable antigenicity. We propose that a system of immunological classification of the parasite can be developed based on the polymorphism of these proteins.

Fine structure of the malaria parasite Plasmodium falciparum in human hepatocytes in vitro

1986 ◽  
Vol 244 (2) ◽  
Author(s):  
JacquesF.G.M. Meis ◽  
P.JosM. Rijntjes ◽  
JanPeter Verhave ◽  
Thivi Ponnudurai ◽  
MichaelR. Hollingdale ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Fine Structure ◽  
Malaria Parasite ◽  
Human Hepatocytes ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum
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