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.
Scientists enlist engineered protein to battle the MERS virus
22.05.2017 | University of Toronto
Insight into enzyme's 3-D structure could cut biofuel costs
19.05.2017 | DOE/Los Alamos National Laboratory
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.
Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...
22.05.2017 | Event News
17.05.2017 | Event News
16.05.2017 | Event News
22.05.2017 | Materials Sciences
22.05.2017 | Life Sciences
22.05.2017 | Physics and Astronomy