Conditional expression of apical membrane antigen 1 in Plasmodium falciparum shows it is required for erythrocyte invasion by merozoites

Cell Microbiol. 2014 May;16(5):642-56. doi: 10.1111/cmi.12287. Epub 2014 Mar 27.

Abstract

Malaria is caused by obligate intracellular parasites, of which Plasmodium falciparum is the most lethal species. In humans, P. falciparum merozoites (invasive forms of the parasite) employ a host of parasite proteins to rapidly invade erythrocytes. One of these is the P. falciparum apical membrane antigen 1 (PfAMA1) which forms a complex with rhoptry neck proteins at the tight junction. Here, we have placed the Pfama1 gene under conditional control using dimerizable Cre recombinase (DiCre) in P. falciparum. DiCre-mediated excision of the loxP-flanked Pfama1 gene results in approximately 80% decreased expression of the protein within one intraerythrocytic growth cycle. This reduces growth by 40%, due to decreased invasion efficiency characterized by a post-invasion defect in sealing of the parasitophorous vacuole. These results show that PfAMA1 is an essential protein for merozoite invasion in P. falciparum and either directly or indirectly plays a role in resealing of the red blood cell at the posterior end of the invasion event.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / metabolism*
  • Endocytosis*
  • Erythrocytes / parasitology*
  • Gene Expression
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Merozoites / physiology*
  • Molecular Biology
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / physiology*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Recombination, Genetic
  • Vacuoles / parasitology*

Substances

  • Antigens, Protozoan
  • Membrane Proteins
  • Protozoan Proteins
  • apical membrane antigen I, Plasmodium