Apical membrane antigen 1 plays a central role in erythrocyte invasion by Plasmodium species

Apical membrane antigen 1 (AMA1) is an asexual blood-stage protein expresse d in the invasive merozoite form of Plasmodia species, which are the causat ive agent of malaria. We have complemented the function of Plasmodium falci parum AMA1 (PfAMA1) with a divergent AMA1 transgene from Plasmodium chabaud i (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 critica l, perhaps essential, for blood-stage growth. Importantly, we showed that P cAMA1 expression in P. falciparum provides trans-species complementation to at least 35% of the function of endogenous PfAMA1 in human red cells. Furt hermore. expression of this transgene in P. falciparum leads to more effici ent invasion of murine erythrocytes. These results indicate an important ro le for AMA1 in the invasion of red blood cells (RBCs) across divergent Plas modium species.