The role of monocarboxylate transporters in Plasmodium falciparum invasion into human red blood cells

Malaria is a life-threatening infectious disease caused by Plasmodium parasites, particularly P. falciparum is responsible for the deadliest form of the disease. One of the protein families involved in invasion process is the reticulocyte binding protein homologues (RH). The interaction between PfRH...

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Bibliographic Details
Main Author: Wong, Ee Lin
Other Authors: Peter Preiser
Format: Final Year Project
Language:English
Published: Nanyang Technological University 2021
Subjects:
Online Access:https://hdl.handle.net/10356/153281
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Institution: Nanyang Technological University
Language: English
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Summary:Malaria is a life-threatening infectious disease caused by Plasmodium parasites, particularly P. falciparum is responsible for the deadliest form of the disease. One of the protein families involved in invasion process is the reticulocyte binding protein homologues (RH). The interaction between PfRH5 ligand and basigin (BSG) receptor was discovered to be essential for merozoite invasion into erythrocytes. Previous studies have elucidated the role of PfRH5-BSG interactions in triggering Ca2+ influx and cytoskeletal modifications in host erythrocytes. BSG is tightly associated with other proteins including monocarboxylate transporters (MCT), a transmembrane carrier protein. In this study, the role of host MCT in merozoite invasion was investigated using a competitive cell-permeable inhibitor, AZD3965. The invasion inhibition assay showed a dose-dependent MCT inhibition on merozoite invasion, indicating that MCT is important for invasion. Furthermore, MCT inhibition led to a reduction in RBC cytosolic Ca2+ level. This suggests that MCT also plays a role in Ca2+ signaling during invasion. Taken together, my findings have provided evidence that host MCT is required for merozoite invasion, and thereby offer new insights into the mechanism of merozoite invasion.