Death by Amoeba, a nibble at a time

20:02
Death by Amoeba, a nibble at a time -
The amoeba E. histolytica (in green) takes a bite out of a human cell (outlined in pink).

Big gulp. Amoeba E. histolytica (green) takes a bite of a human cell (outlined in pink).

Katherine Ralston

Entamoeba histolytica is a small pathogen that takes a terrible toll. The parasite unicellular amoeba about a tenth of the size of a dust mite infects 50 million people worldwide and kills as many as 100,000 each year. Now, a new report reveals how the microbe proved its fatal damage: eating live cells, piece by piece. The discovery provides a potential target for new drugs to treat E. histolytica infections, and transforms the understanding of the researchers how parasites work.

"This process of whittling cells went undetected by all in this area, including me, for over a hundred years," says infectious disease specialist William Petri University of Virginia in Charlottesville, a co-author who has studied E. histolytica for more than two decades.

Although scientists have studied E. histolytica for over a century many of the parasite remains a mystery. part of the problem is that it behaves unpredictably. many infected people have no symptoms at all-amoeba lives quietly in their gut, feeding on bacteria without cause trouble. But in others the parasite attacks the intestine itself and may cause life-threatening diarrhea, ulcers of the intestine, and liver abscesses. This disease called amoebiasis, is a major cause of parasitic death in humans. Common in parts of the developing world, including Africa, Latin America and South Asia, it is transmitted through food and water contaminated. But researchers knew only bits of how the disease plays in the intestine. They knew, for example, that the amoeba has only killed cells with which he had direct contact, and it binds to these cells using specific sugars, called lectins.

"We thought they somehow caused the death of cells and parasites eat the dead cells," says microbiologist Katherine Ralston of the University of Virginia. Because amoebas are known to feed by phagocytosis, a process in which an engulfing cell and "eats" other researchers have speculated amoeba ingested dead cells together.

But Ralston wondered if new live microscopy techniques that allow scientists to capture video cells in action, could be more. Working with Petri and colleagues at the University of Virginia and Jawaharlal Nehru University in New Delhi, Ralston has parasitic amoeba and human cells that have fluorescent made so they would be easier to locate in a dish and examined their interaction. what saw the team surprised.

"It is remarkable to see the amoeba taking bites, "Ralston said. Within a minute of contact, the parasites were torn and ingestion of fragments of human cells, which were visible as bits of fluorescent material in the ameba. The bite was like trogocytosis, a process in which immune cells extract bits of other immune cells, but was unique in that it took place between a parasite and its host and eventually cause cell death. Once the amoeba took his first bite, he continued to consume more and more of the cell until the cell is dead about 10 minutes later.

"A little nibbling caused more snacking," says Ralston, "and this was happening when human cells were alive."

When the cells were dead, amoeba arrested snacking, detached cells, and is past. human red blood cells have the same gruesome end. (See video-human cell appears in pink, green amoeba.) the team then repeated the experiment with fabric intestinal live from mice engineered to have fluorescent intestinal cells and found the parasites have invaded the tissue and caused damage similar to that seen in samples of E. histolytica infected colon tissue human.

the researchers could not be sure that snacking was actually caused the death of cells, however, so they used a drug that interferes with the ability of the amoeba to remodel to bite observe its effect on cell death. Drug amoeba hampered nibbled less and did not kill the cells. Nor amoebas the GM team, so they could not produce the proteins and lectins often found where the parasites come into contact with human cells.

Together, the results suggest that this fragmentary snacking causes cell death and damage often seen in E. histolytica 'of the suite, and that lectins can induce or regulate the behavior of bite, reports the online team today Nature . If further studies confirm that E. histolytica actually kills cells in this way in people suffering from amoebiasis, Ralston said, they could open the way to new treatments for the disease. "If we could understand how the amoeba takes a bite, it would be a good target for therapeutic drugs."

The discovery of the team could change the game E. histolytica research, said Upi Singh, a physician and infectious disease researcher at Stanford University in California who was not involved in the study. "It is fantastic for the area to have a study of this caliber come, "she said." This changes the paradigm. "

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