When a single drop of contaminated water meets the human gut, it can release a master of disguise. Entamoeba histolytica, an amoeba just one cell across, lives quietly in millions of bodies, usually causing only stomach cramps or diarrhea. But in a twist, it can tear through the colon lining, carve abscesses in the liver and even invade the brain or lungs, all while wearing its victims’ own proteins like a cloak.
“It can kill anything you throw at it, any kind of human cell,” says Katherine Ralston, associate professor of microbiology and molecular genetics at UC Davis.
Ralston’s lab overturned the old toxin theory in 2014, showing that the parasite actually bites off pieces of living tissue in a process called trogocytosis. Under a fluorescent microscope, Katherine watched as the amoeba broke human cells into fragments and swallowed them whole.
Those stolen fragments do more than fuel the parasite, they become its armor. In 2022, Ralston discovered that after nibbling on human cells, E. histolytica survives our immune onslaught by donning proteins from our cell membranes. Their new preprint reveals exactly how: the amoeba grabs human proteins CD46 and CD55 and embeds them on its surface, preventing complement proteins from recognizing and killing it.
Tackling this microscopic criminal has required building a toolkit from scratch. Its genome, sequenced in 2005, dwarfs that of many other pathogens, five times larger than salmonella’s and 2,500 times bigger than HIV’s. Only in 2013 did researchers learn that E. histolytica uses RNA interference to regulate its genes. By 2021, Ralston and her team had crafted an RNAi library capable of silencing each of the parasite’s 8,734 genes one at a time.
Now, in the May issue of Trends in Parasitology, Ralston, graduate student Maura Ruyechan and postdoc Wesley Huang map out the next steps: marry RNAi with CRISPR gene editing to tag key proteins with fluorescent markers and delete critical gene segments.
“We now see a light at the end of the tunnel, and we think this could be achievable,” Huang says. With these tools, researchers could pinpoint the parasite’s vulnerabilities and finally design vaccines or drugs to stop it in its tracks.
The study has been published in the journal Trends in Parasitology.
Source: UC Davis
