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Battling a Killer Parasite “The rapid phagocytosis of the cell corpse hides any evidence of the ‘crime’ that has occurred, and may serve to hide the ameba from the immune system,” says Petri. “Our hope is that understanding the process will give us ways to intervene to combat this infection.”
Entamoeba histolytica attacks and kills human immune cells in seconds, then eats the cells’ corpses. The parasite causes amebiasis, an intestinal illness that leads to diarrhea, malnutrition and, in some cases, death. Amebiasis annually affects about 50 million people worldwide and kills nearly 100,000 people each year. PHOTO: Ameba in a human intestine that have eaten dead red blood cells and white cells. The research team, directed by William Petri, Jr., M.D., Ph.D, theorized that identifying molecules involved in the corpse ingestion might provide insight into how the parasite causes colitis in children. The team identified a particular protein on the surface of the ameba, a kinase known as PATMK. Their research was published in the Jan. 18 issue of PLoS Pathogens, a peer-reviewed journal from the Public Library of Science. Using a special technique called RNA interference to inhibit the actions of this kinase, they prevented the ameba from eating dead cells. “By blocking this kinase, we have for the first time prevented the ameba from colonizing and invading the gut,” says Petri, Chief of UVA’s Division of Infectious Diseases and International Health. “This means that we are a step closer to preventing this disease, which wreaks havoc among children worldwide.” Those who survive multiple infections from the parasite, especially children, suffer long-term health consequences, including stunted growth, delayed mental development and weakened immune systems, says microbiology doctoral student Alicia Linford. Researchers hope to defeat the disease the same way other diseases such as measles and polio have been dealt with. “Since there are vaccines for so many other childhood diseases, the idea was to prevent people from becoming infected with the parasite in the first place,” she says. Working with colleagues in Bangladesh, Petri has shown that the parasite causes diarrhea or dysentery in 8 percent of young children worldwide each year. “Infection and further invasion into the gut require the clearance of dead cells in order to prevent immune recognition of the damaged tissue,” says Douglas Boettner, Ph.D., a member of the research team. “PATMK is the first individual member of a large family of proteins to be assigned a function related to the clearance of dying tissue during pathogenesis.” This protein may be a pivotal vaccination target because these preliminary studies show that alterations in PATMK function reduced progression of amebiasis in mice, Boettner adds. “A vaccine that ultimately would prevent this ameba from clearing the damaged host may draw in helpful immune cells, and thus help to clear this infection.” The research team included Boettner, Linford, UVA graduate student Sarah Buss, UVA researcher Eric Houpt, M.D., and Nicholas Sherman, Ph.D., and Christopher D. Huston, M.D., of the University of Vermont. Their work shows how infection depends upon the ameba’s consumption of dead cells. By identifying the molecule that controls eating, scientists are one step closer to the ultimate goal of preventing disease caused by this parasite.
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Research from a University of Virginia Health System-led team may help prevent thousands of deaths annually caused by one of the world’s most voracious parasites.