4D microscopy reveals malaria invasion via erythrocyte membrane vacuole

4D microscopy reveals malaria invasion via erythrocyte membrane vacuole


State-of-the-art video microscopy has enabled researchers to see the molecular details of how malaria parasites invade red blood cells - a key step in the disease.

The researchers used a custom-built lattice light sheet microscope to capture high-resolution videos of individual parasites invading red blood cells, and visualize the molecular and cellular changes that occur throughout this process. The research has provided critical new information about malaria parasite biology that may have applications for the development of much-needed new antimalarial medicines. The research was published in Nature Communications.

An advanced microscopy platform, called lattice light sheet microscopy, has been used to obtain detailed, real-time videos of the malaria parasite invading red blood cells. The research has revealed key steps in the parasite invasion process, which is a critical point of the malaria life-cycle and underpins many symptoms of malaria. The team's discoveries could advance the development of much-needed new antimalarial medicines.

Malaria is a mosquito-borne disease that kills around 400,000 people globally each year. Many of the serious symptoms of malaria occur because of the invasion and growth of the Plasmodium parasite in an infected person's red blood cells, said the senior author.

"Understanding in better detail exactly how the parasite invades red blood cells may reveal new ways to stop this stage of the parasite life cycle, potentially leading to much-needed new therapies," the author said.

"The videos we recorded showed the 'push and pull' interactions as the parasite landed on the red blood cell, and then entered the cell in an enclosed chamber - called a vacuole - where it grew and multiplied. There has long been contention in the field about whether the vacuole is derived from the parasite or the host cell. Our research resolved this question, revealing it was created from the red blood cell's membrane," the author said.

Most antimalarial therapies and vaccines target the initial binding of malaria to red blood cells.

"By visualising these processes in more detail, our research may contribute in several ways to the development of new antimalarial therapies. For example, now that we know that the parasite vacuole relies on components of the red blood cell membrane, it might be possible to target these components with medicines to disrupt the parasite life cycle. This host-directed approach could be one way to bypass the malaria parasite's propensity to rapidly develop drug resistance," the author said.

"LLSM may also have applications for observing the specific steps of parasite invasion that are blocked by potential new drugs - an area we are now very interested in pursuing."

"In the past, the choice of microscope for an experiment had to be a compromise between capturing a lower resolution video, which revealed dynamic processes like shape changes or movement, and capturing much higher-definition still images, which provided much more detail about how the cells and molecules are functioning," the author said.

"LLSM allows us to obtain high-resolution videos of cells, which has been a game-changer for many fields of biological research.

https://www.wehi.edu.au/news/microscopic-cctv-reveals-secrets-malaria-invasion

https://www.nature.com/articles/s41467-021-23626-7

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2F4d-analysis-of-malaria&filter=22

Edited

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