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April 10, 2014

Nibbled to death: UVA discovers new way human cells are killed

University of Virginia School of Medicine researchers studying a potentially deadly parasitic infection have discovered an unknown ways that human cells are killed, with the parasitic amoeba essentially nibbling cells to death as a piranha might attack its prey.

Until now, researchers had assumed that the amoeba, Entamoeba histolytica, killed and then engulfed and consumed human cells. But the UVA research upends that idea, suggesting instead that the amoeba takes small bites of the cell until the cell dies – and then the amoeba loses all interest in eating the corpse.

“This is the first demonstration that nibbling can serve as a way to kill other cells. The findings suggest that amoebae might invade and destroy host intestinal tissue by nibbling alive the cells that line the gut,” said UVA researcher Katherine S. Ralston, PhD. “Intriguingly, there are hints that organisms can also nibble. Perhaps this process is more common than we realize, and it is taken to the extreme in the case of the amoebae, which use nibbling to kill.”

Deadly diarrhea

It’s important to understand Entamoeba histolytica because it causes a potentially fatal diarrhea common in the developing world. Approximately a third of all infants are infected within their first year of life in the Bangladeshi slum where the UVA researchers have been working. The amoebae colonize the colon and begin their nasty work, which can produce diarrhea, inflammation of the colon, bowel diseases or even no symptoms at all.

Rather than poisoning human cells, as has been previously thought, the amoebae appear to nip at the cellular membrane, as a goldfish might nip at another goldfish. Eventually, the amoeba consumes enough of the membrane – the cell’s casing – that the membrane becomes unstable and the cell dies. The amoeba then detaches itself from its dinner and moves on to another, still living meal.

“It has been 111 years exactly since this parasite was named “histolytica” for its ability to lyse tissues. Finally, the way it kills has been discovered,” said William A. Petri Jr., MD, PhD, chief of the UVA Division of Infectious Diseases and International Health. “This provides an avenue to explore how best to prevent and treat this parasite that infects up to one of every three children by their first birthday in Bangladesh.”

The UVA researchers hope that their new findings will help lead to new treatments for amoebiasis, the disease the amoebae cause.

Published in Nature

The findings have been published as a letter in the prestigious journal Nature. The letter was authored by Ralston, of the UVA Department of Medicine; Michael D. Solga, of the UVA Department of Microbiology, Immunology and Cancer Biology; Nicole M. Mackey-Lawrence, of the Department of Medicine; Somlata, of the School of Life Sciences at Jawaharlal Nehru University in New Delhi, India; Alok Bhattacharya of Jawaharlal Nehru; and Petri.

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