Electron tomography of Plasmodium falciparum merozoites reveals core cellular events that underpin erythrocyte invasion

Cell Microbiol. 2013 Sep;15(9):1457-72. doi: 10.1111/cmi.12132. Epub 2013 Mar 22.


Erythrocyte invasion by merozoites forms of the malaria parasite is a key step in the establishment of human malaria disease. To date, efforts to understand cellular events underpinning entry have been limited to insights from non-human parasites, with no studies at sub-micrometer resolution undertaken using the most virulent human malaria parasite, Plasmodium falciparum. This leaves our understanding of the dynamics of merozoite sub-cellular compartments during infectionincomplete, in particular that of the secretory organelles. Using advances in P. falciparum merozoite isolation and new imaging techniques we present a three-dimensional study of invasion using electron microscopy, cryo-electron tomography and cryo-X-ray tomography. We describe the core architectural features of invasion and identify fusion between rhoptries at the commencement of invasion as a hitherto overlooked event that likely provides a critical step that initiates entry. Given the centrality of merozoite organelle proteins to vaccine development, these insights provide a mechanistic framework to understand therapeutic strategies targeted towards the cellular events of invasion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Electron Microscope Tomography*
  • Endocytosis*
  • Erythrocytes / parasitology*
  • Erythrocytes / ultrastructure*
  • Host-Pathogen Interactions
  • Humans
  • Imaging, Three-Dimensional
  • Merozoites / ultrastructure*
  • Plasmodium falciparum / physiology*
  • Plasmodium falciparum / ultrastructure*