Deadly nibbles: UVA researchers’ parasite discovery is big news in global health

This image taken by UVA’s Dr. Katherine Ralston with a microscope shows Entamoeba histolytica parasites (green) ingesting bites of human cells. Image courtesy Nature. This image taken by UVA’s Dr. Katherine Ralston with a microscope shows Entamoeba histolytica parasites (green) ingesting bites of human cells. Image courtesy Nature.

A team of researchers at UVA’s School of Medicine published a big discovery in the journal Nature this month: They’ve figured out how a particularly nasty parasite wreaks havoc in the human intestine, and the findings could go a long way toward treating a widespread and often deadly childhood disease.

Scientists have been studying the gut-dwelling Entamoeba histolytica for more than a century, and with good reason. It’s one of a number of parasitic amoebas that can cause severe diarrhea, an illness that often goes unacknowledged in the developed world as the killer that it is, said Dr. William A. Petri Jr., chief of UVA’s Division of Infectious Diseases and International Health.

“It’s more important than AIDS or tuberculosis or malaria as a cause of death in young children,” Petri said. Only pneumonia kills more children under 5 annually, according to the World Health Organization. For Petri, the problem went from academic to all too real when he traveled to Bangladesh to study the effects of the amoeba disease. In the country’s urban slums, a third of babies are infected with the parasite before their first birthday.

And yet there aren’t many people studying this particular bug. Petri’s team at UVA is one of only four or five in the U.S. tackling it with funding from the National Institutes of Health, he said. Four years ago, Dr. Katherine Ralston, a postdoc in Petri’s lab, noticed something nobody had before.

“She saw something about the way these amoebas kill cells that I had missed entirely,” said Petri. So had everybody else in the century that had elapsed since the parasite was discovered.

Researchers knew Entamoeba didn’t engulf human intestinal cells and eat them, but instead ruptured—lysed—them. They just didn’t know how.

What Ralston saw happening under her light microscope was nibbling. The amoebas were sidling up to human cells and nipping off bits of their membranes, then shuffling off when the cells ultimately broke open, spilled their contents, and died. By applying fluorescent dye, she was able to show the pieces of human cell floating in the amoebas’ insides, and capture the process on camera.

Scientists have observed a similar, if gentler, process called trogocytosis in the interactions of human immune cells, where the membrane touching acts as a kind of communication mechanism.

“What’s new is this discovery that an ancient eukaryote has this capability,” said Petri. “I think what this work suggests is that trogocytosis is probably a more common and ancient process than has ever been known.”

Petri said the reason for the deadly nibbling is still a big question. He and his team have some theories: The amoebas may be killing off the gut’s thin epithelial cell layer in order to penetrate deeper tissue, or the ruptured cells may be releasing potassium channels that cause the diarrhea, thus spreading the disease. They could also be distracting the body’s immune system by leaving the dead hulls of cells floating in the gut for cleanup, which Petri said could explain why the amoeba can live in the human body for months without causing symptoms.

But even if they don’t know the why, they’re already finding ways to stop the process. The study found the nibbling could be blocked with an antibody that targets the “binding port” where the amoeba latches onto human cells. That means a vaccine could be developed to prevent the parasite from doing damage.

And for infectious disease researchers, that’s the real goal. “Everyone in the school of medicine is motivated by the hope that the work we do is going to lead to improvements in human health,” Petri said.