Parasites are known to infect human cells through a variety of ingenious mechanisms. Many of them have even evolved sophisticated strategies to evade a host’s immune system by avoiding it entirely. One type of parasite, Entamoeba histolytica, has developed a very intriguing way to do this. It rips pieces off human cells and steals the proteins to wear them as a disguise.
E. histolytica, a single-celled parasite, is a causative agent of amoebiasis, an alarming cause of illness and death, spreading through the fecal-oral route. Its hardy, dormant cysts can contaminate food and water, survive stomach acid, and break open in the small intestine. What emerges out are active amoebic trophozoites that colonize the large intestine, where they multiply and form new cysts. Both trophozoites and cysts are then passed in the feces to continue the cycle.
This parasite infects around 50 million people each year and proves fatal for nearly 70,000 of them. Usually, it causes nothing more than diarrhea, but in some cases, it liquefies the liver and invades the brain and lungs. Despite the global burden and its impact on human health, E. histolytica has been relatively understudied. Even its basic mechanisms are not well known.
“All parasites are understudied, but E. histolytica is especially enigmatic,” says Katherine Ralston, an associate professor in the Department of Microbiology and Molecular Genetics. “It can kill anything you throw at it, any kind of human cell.”
Researchers have long known that the amoebiasis parasite can kill white blood cells to evade the immune system. However, exactly how it does this was unknown. In the past scientists believed that it killed the cells by injecting some kind of poison.
However, Ralston found something very different. Instead of ingesting cells in such a way that will kill them, this parasite bites chunks off the cells and leaves them wounded. But it doesn’t merely eat these pieces for food; it steals their proteins, namely CD46 and CD55, from the outer membrane of the cell and cloaks them around its own surface. These two proteins are used to shield human cells from being attacked by the immune system.
With the integration of proteins around itself, the immune system’s defenses assume E. histolytica is a part of the host, allowing amoebae to remain invisible. This process of taking another cell's proteins is called trogocytosis.
The discovery was first outlined in a preprint study published late in 2024. Now, a new study advocates using the parasite’s already sequenced RNAi library to identify crucial genes that bite and steal human proteins. By combining it with the gene-editing tool CRISPR, the specific parts could be targeted using drugs, creating a new kind of treatment for this deadly parasite.
“We now see a light at the end of the tunnel, and we think this could be achievable,” says the graduate student Wesley Huang.
The study has been published in Trends in Parasitology.
Source: UC Davis.
