How the malaria parasite feeds inside a red blood cell

2020

Challenge

Malaria is a global killer, particularly for children, causing 200 million cases and more than 400,000 deaths annually. The parasite that causes malaria evades the immune system by hiding inside our own red blood cells, where it has access to all the essential nutrients it needs to grow and reproduce. However, these nutrients must pass through two barriers: the red blood cell’s plasma membrane and a protective sac that surrounds the parasite. Understanding the mechanism that allows nutrients, particularly fats, to pass through these barriers will help scientists develop antimalarial drugs.

Advance

Using a super-powerful electron microscope, IRP researchers led by Joshua Zimmerberg, M.D., Ph.D.,  discovered that some sections of the malaria parasite’s protective sac touch the surface of the parasite, while others are at least 20 nanometers away. They also found fat-transporting molecules in the regions where the parasite and its protective membrane were in very close contact. Finally, they determined that these ‘sticky’ spots where fat nutrients pass through the protective sac are separate from the membrane’s more open, watery spaces, which the scientists had previously discovered were used to transport salts.

Impact

The identification of the sites where fats pass through the malaria parasite’s protective membrane deepens our understanding of how the parasite interacts with red blood cells. Moreover, this advance in our understanding of the protective membrane’s structure and the mechanisms of nutritional transport across the membrane may provide a useful target for antimalarial drugs that interrupt the parasite’s ability to feed, especially since many drugs are fat-soluble.

Publications

Garten, M, Beck, JR, Roth R, Tenkova-Heuser, T, Heuser, J, Istvan, ES, Bleck, CKE, Goldberg, DE, Zimmerberg, J. (2020). Contacting domains segregate a lipid transporter from a solute transporter in the malarial host–parasite interface. Nat Commun. Jul 30;11(1):3825. doi: 10.1038/s41467-020-17506-9.