A parasite that infects 15 to 30 percent of Americans and as many as 90 percent of Europeans may have an Achilles’ heel, a protein essential to its movement within the body, a University of Idaho researcher believes.
That protein in the outer membrane of the parasite Toxoplasma gondii appears unique to the parasite that infects cats, humans and most warm-blooded animals.
Disabling the protein or its effects may stop the parasite before it can enter cells and reproduce, said Gustavo Arrizabalaga, an assistant professor of microbiology, molecular biology and biochemistry at Moscow.
He will use a $729,000 grant from the American Cancer Society to explore the protein’s role in the parasite’s motility, the active event that allows it to move from cell to cell as it moves from the gut or lungs into other organs.
Toxoplasmosis, the disease caused by the infection, threatens pregnant women and people with weak immune systems, particularly those with AIDS or blood cancers such as Hodgkin’s, lymphoma or leukemia, Arrizabalaga said.
For those with weak immune systems, such as the developing fetus or those on chemotherapy, toxoplasmosis can cause severe symptoms and death.
The infection rates are so high among people because the parasite moves easily from felines, most commonly house cats, which carry it in the gut. Contaminated cat litter or garden produce commonly lead to human infections.
Although house cats are a common source of infection, people also become infected by eating animals, particularly sheep and pigs that have been infected. Although cooking destroys the parasite, those who like their lamb or pork medium rare can be infected by the parasite through those durable cysts. A cultural preference for lightly cooked lamb and pork explains the higher infection rates among Europeans, Arrizabalaga said.
Part of the parasite’s success is that its victims’ immune systems rapidly develop defenses to control the parasite, so most victims do not show any symptoms or suffer serious harm.
In response to the healthy immune system, the parasite quickly walls itself off in the form of a durable cyst so it can’t be killed. That cyst remains in the victim’s muscle tissue, brain or other organs for the life of the infected person.
The American Cancer Society-funded work focuses on the hypothesis that the parasite can only move when potassium concentrations are low as in the outside of the host cell and are completely non-motile in high concentrations of potassium like those inside a cell, where the parasite reproduces.
Arrizabalaga works with six mutant forms of the parasite that respond in different ways to potassium concentrations. His research has identified a protein that appears to act as a channel or guide as it detects different potassium levels.
His American Cancer Society focuses on understanding the way the parasite moves and pushes the cell membrane, a critical point in infection.
“If you can stop motility, the parasite will die because it can’t get into a cell,” said Arrizabalaga, who has studied the parasite for nine years.
His work focuses on a key question: “What are the genes and the molecules the parasite uses to tell when to move and when to stop?”
With Arrizabalaga’s grant, the American Cancer Society funds the work of three Idaho researchers, all of them University of Idaho faculty. Kurt Gustin, a microbiologist, studies how viruses hijack cell processes using rhinovirus, the main cause of the common cold, as a model. Gary Daughdrill, a molecular biologist, studies the tumor suppressor protein, p53, and its role in DNA repair.
Arrizabalaga and Gustin were funded through the National Institutes of Health-funded Center of Biomedical Research Excellence on Infectious Disease created by College of Agricultural and Life Sciences researchers in 2000. Daughdrill was hired through an NIH-funded center in the College of Science focused on evolutionary biology.
The centers have drawn more than $40 million in support from the NIH Institutional Development Award program to help Idaho researchers compete for independent funding.
Written by Bill Loftus
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