Comparative spatial proteomics of Plasmodium-infected erythrocytes

Siau, Anthony; Ang, Jing Wen; Sheriff, Omar; Hoo, Regina; Loh, Han Ping; Tay, Donald; Huang, Ximei; Yam, Xue Yan; Lai, Soak Kuan; Meng, Wei; Julca, Irene; Kwan, Sze Siu; Mutwil, Marek; Preiser, Peter R.

doi:10.1016/j.celrep.2023.113419

Cited by 4 publications

(2 citation statements)

References 112 publications

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“…The inhibitory effect of rabbit IgG against P. vivax proteins on erythrocyte invasion through transgenic P. knowlesi lines expressing respective P. vivax antigens was comparable to that of the wild-type P. knowlesi (Ndegwa et al, 2021). Given the numerous P. vivax antigens that still lack characterization (Siau et al, 2023) and the labor-intensive, time-consuming nature of gene editing, wild-type P. knowlesi could be useful in screening P. vivax proteins using an invasion inhibition assay. For the assay's initial step, mature forms of parasitized erythrocytes were enriched from a mix of early-stage parasites and uninfected erythrocytes.…”

Section: Discussionmentioning

confidence: 89%

“…Due to low viscosity, separation using Percoll requires lower centrifugal forces and a shorter experimental duration that might induce greater integrity of the parasites and host cells (Tosta et al, 1980). Regarding the changing density of parasitized erythrocytes according to the maturation of the parasite, we considered that the divergent parasite strains and sources of host cells might result in a different optimal condition of Percoll gradient centrifugation (Tosta et al, 1980;Dluzewski et al, 1984;Reed et al, 2000;Moraes Barros et al, 2017;Ong et al, 2023;Siau et al, 2023); however, reports on P. knowlesi A1-H.1 infecting human erythrocytes are lacking. In this context, we examined various concentrations of Percoll and found that the 40%/70% gradient yielded the best results in terms of high purity and viability of P. knowlesi A1-H.1 schizonts, which were crucial for the downstream invasion inhibition assay (Figure 6).…”

Section: Discussionmentioning

confidence: 99%

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Characterization of merozoite-specific thrombospondin-related anonymous protein (MTRAP) in Plasmodium vivax and P. knowlesi parasites

Sy Thau,

Nguyen,

Truong

et al. 2024

Front. Cell. Infect. Microbiol.

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Plasmodium vivax, the most widespread human malaria parasite, and P. knowlesi, an emerging Plasmodium that infects humans, are the phylogenetically closest malarial species that infect humans, which may induce cross-species reactivity across most co-endemic areas in Southeast Asia. The thrombospondin-related anonymous protein (TRAP) family is indispensable for motility and host cell invasion in the growth and development of Plasmodium parasites. The merozoite-specific TRAP (MTRAP), expressed in blood-stage merozoites, is supposed to be essential for human erythrocyte invasion. We aimed to characterize MTRAPs in blood-stage P. vivax and P. knowlesi parasites and ascertain their cross-species immunoreactivity. Recombinant P. vivax and P. knowlesi MTRAPs of full-length ectodomains were expressed in a mammalian expression system. The MTRAP-specific immunoglobulin G, obtained from immune animals, was used in an immunofluorescence assay for subcellular localization and invasion inhibitory activity in blood-stage parasites was determined. The cross-species humoral immune responses were analyzed in the sera of patients with P. vivax or P. knowlesi infections. The MTRAPs of P. vivax (PvMTRAP) and P. knowlesi (PkMTRAP) were localized on the rhoptry body of merozoites in blood-stage parasites. Both anti-PvMTRAP and anti-PkMTRAP antibodies inhibited erythrocyte invasion of blood-stage P. knowlesi parasites. The humoral immune response to PvMTRAP showed high immunogenicity, longevity, and cross-species immunoreactivity with P. knowlesi. MTRAPs are promising candidates for development of vaccines and therapeutics against vivax and knowlesi malaria.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Characterization of merozoite-specific thrombospondin-related anonymous protein (MTRAP) in Plasmodium vivax and P. knowlesi parasites

Sy Thau,

Nguyen,

Truong

et al. 2024

Front. Cell. Infect. Microbiol.

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Erythrocyte membrane protein 3 (EMAP3) is exposed on the surface of thePlasmodium bergheiinfected red blood cell

Hernandez,

Rashpa,

Jonsdottir

et al. 2024

Preprint

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The human malaria parasitePlasmodium falciparuminvades red blood cells (RBC) and exports parasite proteins to transform the host cell for its survival. These exported proteins facilitate uptake of nutrients and cytoadherence of the infected RBC (iRBC) to endothelial cells of small blood vessels, thus protecting the iRBC from splenic clearance. The parasite protein PfEMP1 and the host protein CD36 play a major role inP. falciparumiRBC cytoadherence. The murine parasitePlasmodium bergheiis a widely used experimental model that combines high genetic tractability with access toin vivostudies.P. berghei iRBC also sequesters in small blood vessels, mediated by binding to CD36. However, the parasite proteins binding to CD36 are unknown and only very few parasite proteins, including EMAP1 and EMAP2, have been identified that are present at the iRBC membrane. We have identified a new protein named EMAP3 and demonstrated its export to the iRBC membrane where it interacts with EMAP1, with only EMAP3 exposed on the outer surface of the iRBC. Parasites lacking EMAP3 display no significant reduction in growth or sequestration, indicating that EMAP3 is not the major CD36-binding protein. The outer-surface location of EMAP3 offers a new scaffold for displayingP. falciparumproteins on the surface of theP. bergheiiRBC, providing a platform to screenin vivoputative inhibitors ofP. falciparumcytoadherence.

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The J Domain Proteins of Plasmodium knowlesi, a Zoonotic Malaria Parasite of Humans

Daniyan,

Singh,

Blatch

2024

IJMS

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Plasmodium knowlesi is a zoonotic form of human malaria, the pathology of which is poorly understood. While the J domain protein (JDP) family has been extensively studied in Plasmodium falciparum, and shown to contribute to malaria pathology, there is currently very limited information on the P. knowlesi JDPs (PkJDPs). This review provides a critical analysis of the literature and publicly available data on PkJDPs. Interestingly, the P. knowlesi genome encodes at least 31 PkJDPs, with well over half belonging to the most diverse types which contain only the signature J domain (type IIIs, 19) or a corrupted version of the J domain (type IVs, 2) as evidence of their membership. The more typical PkJDPs containing other domains typical of JDPs in addition to the J domain are much fewer in number (type IIs, 8; type Is, 2). This study indentifies PkJDPs that are potentially involved in: folding of newly synthesized or misfolded proteins within the P. knowlesi cytosol (a canonical type I and certain typical type IIs); protein translocation (a type III) and folding (a type II) in the ER; and protein import into mitochondria (a type III). Interestingly, a type II PkJDP is potentially exported to the host cell cytosol where it may recruit human HSP70 for the trafficking and folding of other exported P. knowlesi proteins. Experimental studies are required on this fascinating family of proteins, not only to validate their role in the pathology of knowlesi malaria, but also because they represent potential anti-malarial drug targets.

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Comparative spatial proteomics of Plasmodium-infected erythrocytes

Cited by 4 publications

References 112 publications

Characterization of merozoite-specific thrombospondin-related anonymous protein (MTRAP) in Plasmodium vivax and P. knowlesi parasites

Characterization of merozoite-specific thrombospondin-related anonymous protein (MTRAP) in Plasmodium vivax and P. knowlesi parasites

Erythrocyte membrane protein 3 (EMAP3) is exposed on the surface of thePlasmodium bergheiinfected red blood cell

The J Domain Proteins of Plasmodium knowlesi, a Zoonotic Malaria Parasite of Humans

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