Malaria parasite’s skeleton reveals its secrets

The organization of the parasite’s skeleton at an unprecedented scale.

The disease Malaria is caused due to a parasite called Plasmodium. The parasite needs two hosts to complete its life cycle: the Anopheles mosquito and the human. During each stage, the parasite underwent different forms that involve a massive reorganization of the cytoskeleton.

Due to this parasite’s small size, its cytoskeleton has been primarily observable by electron microscopy (EM). In a new study, Two teams from the University of Geneva (UNIGE) have shed new light on the cytoskeleton organization in Plasmodium. 

Using a technique called expansion microscopy, they detailed the organization of the parasite’sparasite’s skeleton at an unprecedented scale.

The cytoskeleton, or cell skeleton, comprises a few filaments’ movements, including actin and tubulin. The network offers rigidity to the cell, allowing the attachment or development of organelles and molecules inside the cell, just as cell distortions. As the parasite changes between developmental stages, its cytoskeleton goes through rehashed, radical rearrangements.

Specifically, the parasite requires a very specific cytoskeleton to move and penetrate the membrane barriers of its host cells, two processes central to the pathogenesis of malaria-causing parasites.

Eloïse Bertiaux, a researcher at UNIGE and the first author of the study, said, “Due to the petite size of Plasmodium—up to 50 times smaller than a human cell—it is a technical challenge to view its cytoskeleton!”

Virginie Hamel, a researcher at the Department of Cell Biology of the Faculty of Sciences of UNIGE and co-leading the study, said, “That is why we adapted our expansion microscopy protocol, which consists of inflating the biological sample while keeping its original shape, so it can be observed at a resolution that has never been attained before.”

Scientists observed the parasite at the ookinete stage, one of the essential stages of Plasmodium development in the mosquito. At the parasite tip, they noticed a structure made of tubulin- similar to a conoid, an organelle involved in host cell invasion, in related Apicomplexa parasites.

Mathieu Brochet, a professor at the Department of Microbiology and Molecular Medicine of the Faculty of Medicine of UNIGE, said“The structure observed in Plasmodium seems, however, divergent and reduced compared with the well-described conoid of Toxoplasma, the parasite causing toxoplasmosis. We still need to determine whether this remnant conoid is also important for host cell invasion of Plasmodium.”

“The discovery of this vestigial conoid highlights the power of expansion microscopy, which can be used to view cytoskeletal structures at the specialized nanoscale need for specialised microscopes. Used in combination with electron microscopy and super-resolution microscopy approaches, this method adds molecular details to the available structural information, paving the way for more in-depth studies of the cytoskeleton organization.”

“This will allow us to gain a better understanding of how Plasmodium invades its host cells, a process that is essential for the pathogenesis of this parasite.”

Journal Reference:
  1. Eloïse Bertiaux et al. Expansion microscopy provides new insights into the cytoskeleton of malaria parasites, including the conservation of a conoid. DOI: 10.1371/journal.pbio.3001020

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