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Published on: May 16, 2013
Apical membrane antigen 1 plays a central role in erythrocyte invasion by Plasmodium species
T Triglia1, J Healer, S R Caruana
1The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia.
Abstract:
Apical membrane antigen 1 (AMA1) is an asexual blood-stage protein expressed in the invasive merozoite form of Plasmodia species, which are the causative agent of malaria. We have complemented the function of Plasmodium falciparum AMA1 (PfAMA1) with a divergent AMA1 transgene from Plasmodium chabaudi (PcAMA1). It was not possible to disrupt the PfAMA1 gene using 'knock-out' plasmids, although we demonstrate that the PfAMA1 gene can be targeted by homologous recombination. These experiments suggest that PfAMA1 is critical, perhaps essential, for blood-stage growth. Importantly, we showed that PcAMA1 expression in P. falciparum provides trans-species complementation to at least 35% of the function of endogenous PfAMA1 in human red cells. Furthermore, expression of this transgene in P. falciparum leads to more efficient invasion of murine erythrocytes. These results indicate an important role for AMA1 in the invasion of red blood cells (RBCs) across divergent Plasmodium species.
Insights
Apical membrane antigen 1 (AMA1) is essential for malaria parasite growth. A related AMA1 protein from another Plasmodium species partially restored function in Plasmodium falciparum, aiding red blood cell invasion.
Area of Science:
- Malariology
- Molecular Parasitology
- Infectious Diseases
Background:
- Apical membrane antigen 1 (AMA1) is crucial for Plasmodium parasites, the causative agents of malaria.
- AMA1 is expressed in merozoites during the asexual blood stage of the malaria parasite lifecycle.
- Understanding AMA1's function is key to developing malaria control strategies.
Purpose of the Study:
- To investigate the essentiality of Plasmodium falciparum AMA1 (PfAMA1) for parasite survival.
- To determine if AMA1 from a divergent species, Plasmodium chabaudi (PcAMA1), can functionally complement PfAMA1.
- To explore the role of AMA1 in red blood cell invasion across different Plasmodium species.
Main Methods:
- Attempted disruption of the PfAMA1 gene using 'knock-out' plasmids.
- Utilized homologous recombination to target the PfAMA1 gene.
- Expressed a PcAMA1 transgene in P. falciparum to assess functional complementation.
Main Results:
- The PfAMA1 gene could not be disrupted, suggesting it is essential for blood-stage growth.
- PcAMA1 expression in P. falciparum partially complemented PfAMA1 function (at least 35%) in human red blood cells.
- The PcAMA1 transgene enhanced P. falciparum invasion of murine erythrocytes.
Conclusions:
- PfAMA1 is critical, likely essential, for the blood-stage development of Plasmodium parasites.
- AMA1 exhibits conserved function in red blood cell invasion across divergent Plasmodium species.
- Cross-species complementation of AMA1 function provides insights into malaria parasite biology and potential therapeutic targets.
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