The skeleton of the malaria disc reveals its mysteries

Plasmodium is the parasite that causes malaria, one of the most deadly parasitic diseases. The parasite needs two guests – the Anopheles mosquito and the human – to complete its life cycle and go through various forms at each stage of its life cycle. Moving from one form to the next involves a major reorganization of the cytoskeleton. Two teams from the University of Geneva (UNIGE) have shed new light on the cytoskeleton group in Plasmodium. Their research, published in Biology PLOS, describing the skeletal organization of the parasite at an unprecedented scale, modifies a recently developed method called magnification microscopy. Cells are “inflated” before imaging, allowing for more structural detail, at the nanometric scale. The study identifies traces of an organelle called a “conoid”, which was thought to be missing in this species despite its importance in attacking closely related parasites.

The cytoskeleton, or cell skeleton, is made up of a network of several types of filaments, including actin and tubulin. It hardens the cell, allowing organelles and molecules to bind or move inside the cell, as well as cell deformations. As the parasite moves between developmental stages, its cytoskeleton reorganises, significantly. In particular, Plasmodium needs a very specific cytoskeleton to move and pass through the membrane barriers in its host cells, two processes that are at the heart of the pathogenesis of malaria-causing parasites. “Because of the very small size of Plasmodium – up to 50 times smaller than a human cell – it’s a technical challenge to see its cytoskeleton!” Begins Eloïse Bertiaux, a researcher at UNIGE and the first author of the study. “That’s why we changed our extension microscopy protocol, which involves incorporating the biological sample while retaining its original shape, and so it can be viewed at an unprecedented mission ”, continues Virginie Hamel, a researcher at the Department of Cell Biology of the UNIGE Faculty of Sciences and co – directing the study.

The researchers saw the parasite at the ookinete level, the form responsible for attacking the midge, a necessary step for the spread of malaria. A structure made of tubulin was visible at the end of the parish. This structure resembles a conoid, an organelle involved in host cell invasion, in associated Apicomplexa parasites. “The structure observed in Plasmodium appears to be differentiated and reduced compared to the well-defined condom of Toxoplasma, the parasite that causes toxoplasmosis. We still need to determine whether the conode is is also important for host cell invasion of Plasmodium ”, explains Mathieu Brochet, professor at the Department of Microbiology and Molecular Medicine of the UNIGE Faculty of Medicine.

The discovery of this vestigial conoid highlights the power of expansion microscopy, which can be used to visualize cytoskeletal structures at the nanoscale without the need for special microscopes. Used in conjunction with electron microscopy and high-resolution microscopy techniques, this method adds molecular detail to the available structural information, paving the way for more in-depth studies of the cytoskeleton. and its molecular group. This will allow us to better understand how Plasmodium attacks its host cells, a process that is essential for the pathogenesis of this parasite.

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