The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake

摘要

Malaria is a life-threatening disease that affects millions of people around the world. The parasites that cause malaria have a complex life cycle that involves infecting both mosquitoes and mammals, including humans. In humans, the parasites spend part of their life cycle inside red blood cells, which causes the symptoms of the disease. In order to survive and multiply, malaria parasites need to make the red blood cell more permeable so that it can absorb nutrients from the blood stream and get rid of the toxic waste products they generate. It remains unclear how the parasites do this, but previous research has shown that the parasites produce channel-like proteins that make red blood cells more permeable to nutrients. One of the proteins involved in this process forms part of a complex with two other proteins, called RhopH2 and RhopH3. It is not known what these other two proteins do, and whether they are necessary for creating the new nutrient channels. Sherling et al. studied the RhopH3 protein to see if it is required to make red blood cells more permeable. The experiments used a genetically modified version of the parasite, in which RhopH3 no longer interacted with the two other proteins. The findings show that RhopH3 has two important roles first, parasites need it to invade the red blood cells, and second, parasites cannot get nutrients into the red blood cell without RhopH3. Most antimalarial drugs work by preventing parasite replication in red blood cells, but parasites are becoming increasingly resistant to these drugs. Understanding which proteins allow parasites to invade and grow within blood cells will further the development of new malaria medication. The next step will be to understand the molecular mechanisms by which RhopH3 promotes invasion and subsequently facilitates nutrient uptake, and will help researchers to explore its potential as a drug target.