Open AccessA thrombospondin structural repeat containing rhoptry protein from P lasmodium falciparum mediates erythrocyte invasion
Author(s) -
Siddiqui Faiza Amber,
Dhawan Shikha,
Singh Shailja,
Singh Bijender,
Gupta Pankaj,
Pandey Alok,
Mohmmed Asif,
Gaur Deepak,
Chitnis Chetan E.
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12118
Subject(s) - microneme , rhoptry , biology , plasmodium falciparum , antibody , thrombospondin , microbiology and biotechnology , apicomplexa , immunology , genetics , metalloproteinase , malaria , matrix metalloproteinase
Summary Host cell invasion by P lasmodium 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 EBA 175 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 EBA 175 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 forthe development of vaccines against blood stage malaria parasites.