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Malaria’s Invasion Imaged

By Stephen Luntz

The process by which the malaria parasite makes its way into red blood cells has been observed in astonishing detail.

Malaria’s Invasion Imaged

The findings, published in Cell Host & Microbe, may help the search for new drugs against the killer disease.

Dr Jake Baum of the Walter and Eliza Hall Institute (WEHI) says the observations required bringing together several lines of work, while developments in super resolution microscopy allowed extraordinarily detailed three-dimensional images of the process.

“Super resolution microscopy has opened up a new realm of understanding into how malaria parasites actually invade the human red blood cell,” Baum says. “Whilst we have observed this miniature parasite drive its way into the cell before, the beauty of the new imaging technology is that it provides a quantum leap in the amount of detail we can see, revealing key molecular and cellular events required for each stage of the invasion process.”

However, the imaging technology was only one part of the challenge. The malaria parasite needed to be isolated in its free form, and it was only recently that WEHI was part of the first isolation of large numbers of parasites outside cells.

Furthermore, while super resolution microscopy provided the most impressive images, Baum says that other technologies were used in combination, including “fluorescence microscopy to give a more holistic view of the cell, with fantastic localisation of proteins”.

The observations revealed that malaria inserts a ring of actin proteins into a red blood cell and then enters through this. Baum compares this to “a thief inserting a window in a house, opening it up and walking through it”.

A similar process has been observed with the Toxoplasma parasite, so this part of the process was not entirely surprising. However, the observation has encouraged the idea that actin should be targeted in the quest to defeat malaria.

Baum also notes that malaria’s entry into cells is “much cleaner” than Toxoplasma, with the invasion done in a “single process”.

A more unexpected finding relates to the way that malaria sheds its fuzzy coat when entering cells. A protease molecule is used to remove the coat, but the observations suggest that the coating is cut off immediately before the parasite enters a cell, with the coat physically removed as the parasite slides through the window into the cell.

Baum says the observations suggest that the entry process “only has one checkpoint”. Once the parasite has started to enter the cell it simply keeps going, whatever obstacles it may encounter. He thinks this discovery may prove useful in finding ways to disrupt the parasite that might have been less effective if dealing with an invader that stopped and tried a new approach when confronted with difficulties.