scholarly journals Distinct Trafficking and Localization of STEVOR Proteins in Three Stages of the Plasmodium falciparum Life Cycle

2004 ◽  
Vol 72 (11) ◽  
pp. 6597-6602 ◽  
Author(s):  
Louisa McRobert ◽  
Peter Preiser ◽  
Sarah Sharp ◽  
William Jarra ◽  
Mallika Kaviratne ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Asexual Parasite ◽  
Reading Frame ◽  
Trafficking Pathway ◽  
Erythrocyte Plasma Membrane ◽  
Three Stages ◽  
Sexual Stages ◽  
Maurer's Clefts ◽  
Subtelomeric Regions

ABSTRACT The genome of Plasmodium falciparum harbors three extensive multigene families, var, rif, and stevor (for subtelomeric variable open reading frame), located mainly in the subtelomeric regions of the parasite's 14 chromosomes. STEVOR variants are known to be expressed in asexual parasites, but no function has as yet been ascribed to this protein family. We have examined the expression of STEVOR proteins in intraerythrocytic sexual stages, gametocytes, and extracellular sporozoites isolated from infected Anopheles mosquitoes. In gametocytes, stevor transcripts appear transiently early in development but STEVOR proteins persist for several days and are transported out of the parasite, travel through the host cell cytoplasm, and localize to the erythrocyte plasma membrane. In contrast to asexual parasites, gametocytes move STEVOR to the periphery via a trafficking pathway independent of Maurer's clefts. In sporozoites, STEVOR appear dispersed throughout the cytoplasm in vesicle-like structures. The pattern of STEVOR localization we have observed in gametocytes and sporozoites differs significantly from that in asexual parasite stages. STEVOR variants are therefore likely to perform different functions in each stage of the parasites life cycle in which they occur.

scholarly journals Plasmodium falciparum sexual parasites regulate infected erythrocyte permeability

2020 ◽  
Author(s):  
Guillaume Bouyer ◽  
Daniela Barbieri ◽  
Florian Dupuy ◽  
Anthony Marteau ◽  
Abdoulaye Sissoko ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Infected Erythrocyte ◽  
Drug Uptake ◽  
Camp Signaling ◽  
Asexual Parasite ◽  
Artemisinin Derivatives ◽  
Mature Gametocyte ◽  
Pde Inhibitors ◽  
Sexual Stages ◽  
Camp Levels

ABSTRACTTo ensure the transport of nutrients necessary for their survival, Plasmodium falciparum parasites increase erythrocyte permeability to diverse solutes. These New Permeation Pathways (NPP) have been extensively characterized in the pathogenic asexual parasite stages, however the existence of NPP has never been investigated in gametocytes, the sexual stages responsible for transmission to mosquitoes. Here, we show that NPP are still active in erythrocytes infected with immature gametocytes and that this activity declines along gametocyte maturation. Our results indicate that NPP are regulated by cyclic AMP (cAMP) signaling cascade during sexual parasite stages, and that the decrease in cAMP levels in mature stages results in a slowdown of NPP activity. We also show that NPP facilitate the uptake of artemisinin derivatives and that phosphodiesterase (PDE) inhibitors can reactivate NPP and increase drug uptake in mature gametocyte-infected erythrocytes. These processes are predicted to play a key role in P. falciparum gametocyte biology and susceptibility to antimalarials.

scholarly journals Plasmodium falciparum sexual parasites regulate infected erythrocyte permeability

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Guillaume Bouyer ◽  
Daniela Barbieri ◽  
Florian Dupuy ◽  
Anthony Marteau ◽  
Abdoulaye Sissoko ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Infected Erythrocyte ◽  
Drug Uptake ◽  
Camp Signaling ◽  
Signaling Cascade ◽  
Asexual Parasite ◽  
Artemisinin Derivatives ◽  
Pde Inhibitors ◽  
Sexual Stages ◽  
Camp Levels

AbstractTo ensure the transport of nutrients necessary for their survival, Plasmodium falciparum parasites increase erythrocyte permeability to diverse solutes. These new permeation pathways (NPPs) have been extensively characterized in the pathogenic asexual parasite stages, however the existence of NPPs has never been investigated in gametocytes, the sexual stages responsible for transmission to mosquitoes. Here, we show that NPPs are still active in erythrocytes infected with immature gametocytes and that this activity declines along gametocyte maturation. Our results indicate that NPPs are regulated by cyclic AMP (cAMP) signaling cascade, and that the decrease in cAMP levels in mature stages results in a slowdown of NPP activity. We also show that NPPs facilitate the uptake of artemisinin derivatives and that phosphodiesterase (PDE) inhibitors can reactivate NPPs and increase drug uptake in mature gametocytes. These processes are predicted to play a key role in P. falciparum gametocyte biology and susceptibility to antimalarials.

scholarly journals Plasmodium falciparumgametocytes: with a view to a kill

Parasitology ◽  
2013 ◽  
Vol 140 (14) ◽  
pp. 1718-1734 ◽  
Author(s):  
ALICE S. BUTTERWORTH ◽  
TINA S. SKINNER-ADAMS ◽  
DON L. GARDINER ◽  
KATHARINE R. TRENHOLME
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Discovery ◽  
Malaria Control ◽  
Asexual Parasite ◽  
Malaria Parasites ◽  
Gametocyte Carriage ◽  
Control Programmes ◽  
Development Pipeline ◽  
Malaria Eradication ◽  
Sexual Stages

SUMMARYDrugs that kill or inhibit the sexual stages ofPlasmodiumin order to prevent transmission are important components of malaria control programmes. Reducing gametocyte carriage is central to the control ofPlasmodium falciparumtransmission as infection can result in extended periods of gametocytaemia. Unfortunately the number of drugs with activity against gametocytes is limited. Primaquine is currently the only licensed drug with activity against the sexual stages of malaria parasites and its use is hampered by safety concerns. This shortcoming is likely the result of the technical challenges associated with gametocyte studies together with the focus of previous drug discovery campaigns on asexual parasite stages. However recent emphasis on malaria eradication has resulted in an upsurge of interest in identifying compounds with activity against gametocytes. This review examines the gametocytocidal properties of currently available drugs as well as those in the development pipeline and examines the prospects for discovery of new anti-gametocyte compounds.

scholarly journals Small Variant STEVOR Antigen Is Uniquely Located within Maurer's Clefts in Plasmodium falciparum-Infected Red Blood Cells

2002 ◽  
Vol 1 (6) ◽  
pp. 926-935 ◽  
Author(s):  
M. Kaviratne ◽  
S. M. Khan ◽  
W. Jarra ◽  
P. R. Preiser
Keyword(s):  
Plasmodium Falciparum ◽  
Multigene Family ◽  
Infected Erythrocyte ◽  
Asexual Parasite ◽  
Parasite Life Cycle ◽  
Host Parasite Interactions ◽  
Erythrocyte Surface ◽  
Maurer's Clefts ◽  
Host Parasite ◽  
Parasite Populations

ABSTRACT Malaria parasite antigens encoded by multigene families are important factors in virulence and in disease pathology. In Plasmodium falciparum, the virulence factor PfEMP-1 is encoded by the var multigene family and is exposed at the infected erythrocyte surface. PfEMP-1 is clonally variant, allowing the parasite to evade host immunity. The recently identified P. falciparum stevor multigene family and its products also have the potential to be involved in similar important aspects of host-parasite interactions. Here, we show tightly regulated stage-specific transcription of stevor occurring over just a few hours of the asexual parasite life cycle. Only a subset of stevor genes are transcribed in parasite populations maintained in cultures and in single micromanipulated parasites. Antibodies against STEVOR recognize proteins of the expected size (∼37 kDa) and localize STEVOR in Maurer's clefts, unique membranous structures located in the cytoplasm of infected erythrocytes. The fact that the timing of stevor expression and the location of STEVOR are clearly distinct from those of other parasite variant antigens suggests that this gene family may have a novel role in P. falciparum biology.

scholarly journals Trafficking and Association of Plasmodium falciparum MC-2TM with the Maurer’s Clefts

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 431
Author(s):  
Raghavendra Yadavalli ◽  
John W. Peterson ◽  
Judith A. Drazba ◽  
Tobili Y. Sam-Yellowe
Keyword(s):  
Plasmodium Falciparum ◽  
Erythrocyte Membrane ◽  
Sodium Carbonate ◽  
Infected Erythrocyte ◽  
Brefeldin A ◽  
Specific Expression ◽  
Lipid Interactions ◽  
And Topology ◽  
Streptolysin O ◽  
Maurer's Clefts

In this study, we investigated stage specific expression, trafficking, solubility and topology of endogenous PfMC-2TM in P. falciparum (3D7) infected erythrocytes. Following Brefeldin A (BFA) treatment of parasites, PfMC-2TM traffic was evaluated using immunofluorescence with antibodies reactive with PfMC-2TM. PfMC-2TM is sensitive to BFA treatment and permeabilization of infected erythrocytes with streptolysin O (SLO) and saponin, showed that the N and C-termini of PfMC-2TM are exposed to the erythrocyte cytoplasm with the central portion of the protein protected in the MC membranes. PfMC-2TM was expressed as early as 4 h post invasion (hpi), was tightly colocalized with REX-1 and trafficked to the erythrocyte membrane without a change in solubility. PfMC-2TM associated with the MC and infected erythrocyte membrane and was resistant to extraction with alkaline sodium carbonate, suggestive of protein-lipid interactions with membranes of the MC and erythrocyte. PfMC-2TM is an additional marker of the nascent MCs.

scholarly journals Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yifat Ofir-Birin ◽  
Hila Ben Ami Pilo ◽  
Abel Cruz Camacho ◽  
Ariel Rudik ◽  
Anna Rivkin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Cerebral Malaria ◽  
Survival Strategy ◽  
Parasitic Disease ◽  
Malaria Parasites ◽  
Sensing System ◽  
Rich Domain ◽  
Cargo Delivery ◽  
Low Levels

AbstractPathogens are thought to use host molecular cues to control when to initiate life-cycle transitions, but these signals are mostly unknown, particularly for the parasitic disease malaria caused by Plasmodium falciparum. The chemokine CXCL10 is present at high levels in fatal cases of cerebral malaria patients, but is reduced in patients who survive and do not have complications. Here we show a Pf ‘decision-sensing-system’ controlled by CXCL10 concentration. High CXCL10 expression prompts P. falciparum to initiate a survival strategy via growth acceleration. Remarkably, P. falciparum inhibits CXCL10 synthesis in monocytes by disrupting the association of host ribosomes with CXCL10 transcripts. The underlying inhibition cascade involves RNA cargo delivery into monocytes that triggers RIG-I, which leads to HUR1 binding to an AU-rich domain of the CXCL10 3’UTR. These data indicate that when the parasite can no longer keep CXCL10 at low levels, it can exploit the chemokine as a cue to shift tactics and escape.

scholarly journals Interaction of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Malabika Chakrabarti ◽  
Nishant Joshi ◽  
Geeta Kumari ◽  
Preeti Singh ◽  
Rumaisha Shoaib ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Specific Protein ◽  
Parasite Growth ◽  
Growth And Survival ◽  
Apicomplexan Parasites ◽  
Parasite Replication ◽  
Main Components ◽  
Β Tubulin

AbstractCytoskeletal structures of Apicomplexan parasites are important for parasite replication, motility, invasion to the host cell and survival. Apicortin, an Apicomplexan specific protein appears to be a crucial factor in maintaining stability of the parasite cytoskeletal assemblies. However, the function of apicortin, in terms of interaction with microtubules still remains elusive. Herein, we have attempted to elucidate the function of Plasmodium falciparum apicortin by monitoring its interaction with two main components of parasite microtubular structure, α-tubulin-I and β-tubulin through in silico and in vitro studies. Further, a p25 domain binding generic drug Tamoxifen (TMX), was used to disrupt PfApicortin-tubulin interactions which led to the inhibition in growth and progression of blood stage life cycle of P. falciparum.

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