Defining the Essential Exportome of the Malaria Parasite

Jonsdottir, Thorey K; Gabriela, Mikha; Crabb, Brendan S.; Koning-Ward, Tania F. de; Gilson, Paul R.

doi:10.1016/j.pt.2021.04.009

Cited by 43 publications

(55 citation statements)

References 84 publications

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“…In order to adapt to the host environment, malaria parasites excrete many proteins to the erythrocyte surface to alter the permeability and adhesion of the erythrocytes. The cell remodeling process aids in intracellular iron homeostasis and nutrient uptake to maintain parasite development ( Yam et al, 2017 ; Beck and Ho, 2021 ; Jonsdottir et al, 2021 ). The most common exported proteins include knob associated histidine rich protein (KAHRP), ring-infected erythrocyte surface antigen (RESA), the Plasmodium helical interspersed subtelomeric-domain proteins (PHIST), and exported protein family (EPF) ( Warncke et al, 2016 ; Matthews et al, 2019 ; Warncke and Beck, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

PfAP2-EXP2, an Essential Transcription Factor for the Intraerythrocytic Development of Plasmodium falciparum

Shang

Wang

Шен

et al. 2022

Front. Cell Dev. Biol.

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Plasmodium falciparum undergoes a series of asexual replications in human erythrocytes after infection, which are effective targets for combatting malaria. Here, we report roles of an ApiAP2 transcription factor PfAP2-EXP2 (PF3D7_0611200) in the intraerythrocytic developmental cycle of P. falciparum. PfAP2-EXP2 conditional knockdown resulted in an asexual growth defect but without an appreciable effect on parasite morphology. Further ChIP-seq analysis revealed that PfAP2-EXP2 targeted genes related to virulence and interaction between erythrocytes and parasites. Especially, PfAP2-EXP2 regulation of euchromatic genes does not depend on recognizing specific DNA sequences, while a CCCTAAACCC motif is found in its heterochromatic binding sites. Combined with transcriptome profiling, we suggest that PfAP2-EXP2 is participated in the intraerythrocytic development by affecting the expression of genes related to cell remodeling at the schizont stage. In summary, this study explores an ApiAP2 member plays an important role for the P. falciparum blood-stage replication, which suggests a new perspective for malaria elimination.

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Section: Discussionmentioning

confidence: 99%

PfAP2-EXP2, an Essential Transcription Factor for the Intraerythrocytic Development of Plasmodium falciparum

Shang

Wang

Шен

et al. 2022

Front. Cell Dev. Biol.

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“…P. falciparum exports a substantial number of proteins to acquire nutrients, modify iRBC membrane properties and avoid the immune system to promote its own survival within the PVM. Once the exported proteins cross the PVM they are transported from the cytoplasm to the iRBC membrane by novel parasite-derived membrane structures, such as the tubovesicular network (TVN), Maurer’s clefts, K-dots, J-dots and exosome-like vesicles that work as a sorting point from which parasite proteins are deposited underneath or into the iRBC membrane ( Figures 2H–K ) ( Jonsdottir et al., 2021 ).…”

Section: Remodelling Red Blood Cells For Parasite Survivalmentioning

confidence: 99%

“…It has novel organelles, such as apicoplast, a modified lysosome (digestive vacuole), and apical organelles (rhoptries, micronemes, dense granules and exoneme) involved in the entry to RBC ( Figure 2A ); however, an infected RBC is devoid of organelles and cellular machinery ( Hanssen et al., 2010 ). Successful P. falciparum growth and division inside RBC therefore requires structural, biochemical and functional modifications to facilitate communication with the extracellular environment ( Jonsdottir et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

The Cellular and Molecular Interaction Between Erythrocytes and Plasmodium falciparum Merozoites

Molina-Franky

Patarroyo

Kalkum

2022

Front. Cell. Infect. Microbiol.

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Plasmodium falciparum is the most lethal human malaria parasite, partly due to its genetic variability and ability to use multiple invasion routes via its binding to host cell surface receptors. The parasite extensively modifies infected red blood cell architecture to promote its survival which leads to increased cell membrane rigidity, adhesiveness and permeability. Merozoites are initially released from infected hepatocytes and efficiently enter red blood cells in a well-orchestrated process that involves specific interactions between parasite ligands and erythrocyte receptors; symptoms of the disease occur during the life-cycle’s blood stage due to capillary blockage and massive erythrocyte lysis. Several studies have focused on elucidating molecular merozoite/erythrocyte interactions and host cell modifications; however, further in-depth analysis is required for understanding the parasite’s biology and thus provide the fundamental tools for developing prophylactic or therapeutic alternatives to mitigate or eliminate Plasmodium falciparum-related malaria. This review focuses on the cellular and molecular events during Plasmodium falciparum merozoite invasion of red blood cells and the alterations that occur in an erythrocyte once it has become infected.

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“…Host cell remodeling is critical for successful Plasmodium replication inside erythrocytes and achieved by targeted export of parasite-encoded proteins. Therefore, the parasite exports a large set of proteins to remodel the host erythrocyte, which is particularly important for plasma membrane fluidity and adhesive properties ( Jonsdottir et al, 2021 ). The repertoire of exported proteins, termed exportome, is estimated to be approximately 10% of the Plasmodium proteome, and a quarter of the exported proteins are likely essential for parasite survival during blood stage development ( Maier et al, 2008 ; Spielmann and Gilberger, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Absence of PEXEL-Dependent Protein Export in Plasmodium Liver Stages Cannot Be Restored by Gain of the HSP101 Protein Translocon ATPase

et al. 2021

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Host cell remodeling is critical for successful Plasmodium replication inside erythrocytes and achieved by targeted export of parasite-encoded proteins. In contrast, during liver infection the malarial parasite appears to avoid protein export, perhaps to limit exposure of parasite antigens by infected liver cells. HSP101, the force-generating ATPase of the protein translocon of exported proteins (PTEX) is the only component that is switched off during early liver infection. Here, we generated transgenic Plasmodium berghei parasite lines that restore liver stage expression of HSP101. HSP101 expression in infected hepatocytes was achieved by swapping the endogenous promoter with the ptex150 promoter and by inserting an additional copy under the control of the elongation one alpha (ef1α) promoter. Both promoters drive constitutive and, hence, also pre-erythrocytic expression. Transgenic parasites were able to complete the life cycle, but failed to export PEXEL-proteins in early liver stages. Our results suggest that PTEX-dependent early liver stage export cannot be restored by addition of HSP101, indicative of alternative export complexes or other functions of the PTEX core complex during liver infection.

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Defining the Essential Exportome of the Malaria Parasite

Cited by 43 publications

References 84 publications

PfAP2-EXP2, an Essential Transcription Factor for the Intraerythrocytic Development of Plasmodium falciparum

PfAP2-EXP2, an Essential Transcription Factor for the Intraerythrocytic Development of Plasmodium falciparum

The Cellular and Molecular Interaction Between Erythrocytes and Plasmodium falciparum Merozoites

Absence of PEXEL-Dependent Protein Export in Plasmodium Liver Stages Cannot Be Restored by Gain of the HSP101 Protein Translocon ATPase

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