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A Simple Protocol for Platelet-mediated Clumping of Plasmodium falciparum-infected Erythrocytes in a Resource Poor Setting
Published on: May 16, 2013
A thrombospondin structural repeat containing rhoptry protein from Plasmodium falciparum mediates erythrocyte
Faiza Amber Siddiqui1, Shikha Dhawan, Shailja Singh
1Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Abstract:
Host cell invasion by Plasmodium falciparum requires multiple molecular interactions between host receptors and parasite ligands. A family of parasite proteins, which contain the conserved thrombospondin structural repeat motif (TSR), has been implicated in receptor binding during invasion. In this study we have characterized the functional role of a TSR containing blood stage protein referred to as P. falciparum thrombospondin related apical merozoite protein (PfTRAMP). Both native and recombinant PfTRAMP bind untreated as well as neuraminidase, trypsin or chymotrypsin-treated human erythrocytes. PfTRAMP is localized in the rhoptry bulb and is secreted during invasion. Adhesion of microneme protein EBA175 with its erythrocyte receptor glycophorin A provides the signal that triggers release of PfTRAMP from the rhoptries. Rabbit antibodies raised against PfTRAMP block erythrocyte invasion by P. falciparum suggesting that PfTRAMP plays an important functional role in invasion. Combination of antibodies against PfTRAMP with antibodies against microneme protein EBA175 provides an additive inhibitory effect against invasion. These observations suggest that targeting multiple conserved parasite ligands involved in different steps of invasion may provide an effective strategy for the development of vaccines against blood stage malaria parasites.
Insights
The malaria parasite Plasmodium falciparum uses PfTRAMP, a thrombospondin repeat motif protein, to invade host cells. Antibodies targeting PfTRAMP and EBA175 show promise for malaria vaccine development.
Area of Science:
- Malariology
- Parasitology
- Molecular Biology
Background:
- Host cell invasion by Plasmodium falciparum is crucial for malaria pathogenesis.
- Parasite ligands interacting with host receptors mediate this invasion process.
- Thrombospondin structural repeat motif (TSR) containing proteins are implicated in Plasmodium falciparum invasion.
Purpose of the Study:
- To characterize the functional role of P. falciparum thrombospondin related apical merozoite protein (PfTRAMP) in host cell invasion.
- To investigate the secretion and binding properties of PfTRAMP.
- To evaluate the potential of PfTRAMP as a vaccine target.
Main Methods:
- Characterization of native and recombinant PfTRAMP binding to human erythrocytes.
- Localization studies of PfTRAMP within the parasite.
- Inhibition assays using antibodies against PfTRAMP and EBA175.
Main Results:
- PfTRAMP binds to both untreated and treated human erythrocytes.
- PfTRAMP is secreted from the rhoptries during invasion, triggered by EBA175-glycophorin A interaction.
- Antibodies against PfTRAMP inhibit P. falciparum invasion, with an additive effect when combined with anti-EBA175 antibodies.
Conclusions:
- PfTRAMP plays a significant role in Plasmodium falciparum erythrocyte invasion.
- Targeting multiple conserved parasite ligands, like PfTRAMP and EBA175, offers a potential strategy for malaria vaccine development.
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