Apical membrane antigen 1 mediates apicomplexan parasite attachment but is dispensable for host cell invasion

Nat Commun. 2013:4:2552. doi: 10.1038/ncomms3552.

Abstract

Apicomplexan parasites invade host cells by forming a ring-like junction with the cell surface and actively sliding through the junction inside an intracellular vacuole. Apical membrane antigen 1 is conserved in apicomplexans and a long-standing malaria vaccine candidate. It is considered to have multiple important roles during host cell penetration, primarily in structuring the junction by interacting with the rhoptry neck 2 protein and transducing the force generated by the parasite motor during internalization. Here, we generate Plasmodium sporozoites and merozoites and Toxoplasma tachyzoites lacking apical membrane antigen 1, and find that the latter two are impaired in host cell attachment but the three display normal host cell penetration through the junction. Therefore, apical membrane antigen 1, rather than an essential invasin, is a dispensable adhesin of apicomplexan zoites. These genetic data have implications on the use of apical membrane antigen 1 or the apical membrane antigen 1-rhoptry neck 2 interaction as targets of intervention strategies against malaria or other diseases caused by apicomplexans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan / genetics*
  • Antigens, Protozoan / metabolism
  • Conserved Sequence
  • Female
  • Gene Deletion
  • Gene Expression
  • Host-Parasite Interactions*
  • Malaria / parasitology
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Plasmodium berghei / genetics*
  • Plasmodium berghei / metabolism
  • Plasmodium berghei / pathogenicity
  • Protein Binding
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Toxoplasma / genetics*
  • Toxoplasma / metabolism
  • Toxoplasma / pathogenicity
  • Toxoplasmosis / parasitology

Substances

  • AMA1 protein, Toxoplasma gondii
  • Antigens, Protozoan
  • Membrane Proteins
  • Protozoan Proteins
  • apical membrane antigen I, Plasmodium
  • rhoptry neck protein 2, Toxoplasma gondii
  • rhoptry-associated antigen-2, Plasmodium