In a study published in Cell Host & Microbe, scientists show that the ROP18 protein disables host cell proteins that would otherwise pop a protective bubble the parasite makes for itself. The parasite puts the bubble on like a spacesuit by forming a membrane around itself when it enters host cells. This protects it from the hostile environment inside the cell, which would otherwise kill it.
“If we can find therapies that block ROP18 and other parasite proteins like it, that could give the host the upper hand in the battle against infection,” says first author Sarah Fentress, a graduate student in the laboratory of L. David Sibley, PhD, professor of molecular microbiology.
Infection with Toxoplasma, or toxoplasmosis, is most familiar to the general public from the recommendation that pregnant women avoid changing cat litter. Cats are commonly infected with the parasite, as are some livestock and wildlife.
“The exact role of ROP18 and related proteins in human disease remains to be studied,” says Sibley. “But mice are natural hosts of Toxoplasma, so studies in laboratory mice are relevant to the spread of infection.”
Epidemiologists estimate that as many as one in every four humans is infected with Toxoplasma. Infections typically cause serious disease only in patients with weakened immune systems. In some rare cases, though, infection in patients with healthy immune systems leads to serious eye or central nervous system disease, or congenital defects or death in the fetuses of pregnant women.
In the new study, Fentress showed that the ROP18 protein binds to a class of host proteins known as immunity-related GTPases. Tests in cell cultures and animal models showed that this binding leads to a reaction that disables the GTPases, which normally would rupture the parasite's protective membrane.
“With one exception, humans don’t have the same family of immunity-related GTPases,” Fentress notes. “But we do have a similar group of immune recognition proteins called guanylate-binding proteins, and we are currently testing to see if ROP18 deactivates these proteins in human cells in a similar manner.”
The findings could be applicable to other parasites and pathogens. Toxoplasmosis belongs to a family of parasites that includes the parasite Plasmodium, which causes malaria. All surround themselves with protective membranes when they enter host cells.
“Plasmodium doesn’t make ROP18, but it does secrete related proteins called FIKK,” says Fentress. “It’s possible they also act to thwart host defense mechanisms like GTPases and guanylate-binding proteins.”
Fentress SJ, Behnke MS, Dunay Ir, Mashayekhi M, Rommereim LM, Fox BA, Bzik DJ, Taylor GA, Turk BE, Lichti CF, Townsend RR, Qiu W, Hui R, Beatty WL, Sibley LD. Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence. Cell Host & Microbe, Dec. 22, 2010.
This research was supported by the National Institutes of Health and the Veteran’s Administration.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.
Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg
Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
19.10.2017 | Materials Sciences
19.10.2017 | Materials Sciences
19.10.2017 | Physics and Astronomy