Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Single protein can determine severity of toxoplasma infections

21.12.2006
The unusual ability of the organism Toxoplasma to infect and reproduce inside almost all warm-blooded animals has led scientists to wonder about the tricks it uses so successfully to subvert the behavior of cells.

Now, a team of Stanford University School of Medicine researchers, led by John Boothroyd, PhD, has shown for the first time how Toxoplasma manages to be so effective: They documented how it injects a particular protein into the cell it infects and how that protein then travels to the cell's nucleus - where it blocks the cell's normal response to invasion.

Never before have researchers offered such insight into the way this type of parasite can hijack a host cell's genetic machinery for its own benefit. And the discovery has wide-ranging implications for a number of diseases caused by other parasites in this class, which reproduce only inside of cells, including the parasite that causes malaria.

The results will be published in the Dec. 20 edition of Nature. They come on the heels of another paper from Boothroyd's lab, published earlier in December in the journal Science, identifying two proteins that can determine how much damage the parasite Toxoplasma can inflict on an animal. Boothroyd is a professor of microbiology and immunology at the School of Medicine.

... more about:
»Boothroyd »Kinase »ROP16 »Toxoplasma »parasite

The latest findings reveal a new mechanism for how an intracellular pathogen can interact with its host, and they may help to explain important differences in how various Toxoplasma strains have evolved to exploit this interaction, said Susan Coller, PhD, one of the study's lead authors who was a postdoctoral scholar in Boothroyd's lab when the work was done.

What shocked the researchers was that a single protein was responsible for the dramatic differences between the strains; they had expected it to be much more complex.

"That it travels to the host cell nucleus is the cherry on the sundae," Coller said. "It's the heart of the cell, the ultimate prize. If you want to affect the cell in a dramatic way, go straight there."

The researchers found that Toxoplasma injects a protein called ROP16 into the host cell. ROP16 is a class of enzyme called a kinase, which is a mediator of cellular messages. Kinases are used by all cells to regulate a variety of key physiological processes, including responding to the presence of an invader. Injecting kinases is an extremely efficient way for a parasite to co-opt a host cell for its own purposes, Boothroyd said.

According to the study, different forms of the injected kinase have dramatically different effects on how a host cell responds to the invading parasite. Knowing what determines the extent of the immune response may allow for therapeutic manipulations, perhaps leading to physicians being able to tune down a response that's out of control in some cases of toxoplasmosis. Although Toxoplasma infections in humans are often asymptomatic, they can cause severe problems in isolated cases, particularly for individuals with compromised immune systems and for fetuses.

In North America and Europe, there are three main strains of Toxoplasma. Experiments have shown that the effects on mice infected with Toxoplasma are highly dependent on the type of strain. Recent results indicate that differences in infection might exist in humans too.

"When you look at the three different strains under the microscope, you can't distinguish them, yet they have such different properties," said the article's other lead author, Jeroen Saeij, PhD, a postdoctoral scholar in Boothroyd's laboratory. "Trying to find which parasite genes are responsible is like solving a puzzle."

The researchers sought to test the hypothesis that some of the strain-specific differences are a result of how the strains interact with the host cell. To do this, the researchers looked for large changes in the gene expression of the hosts - in this case, human cells - when they became infected.

The team used microarrays to examine the entire human genome's response to infection of cells with Toxoplasma. They pinpointed a number of genes involved in the immune response that were activated after being exposed to the parasite. Then, through a series of logical assumptions, they identified the Toxoplasma protein ROP16 as the culprit for causing the immunological changes in human cells. A key point is that it was responsible for the strain-specific differences in how the host cell responded to infection.

Each version of the ROP16 gene evolved to tweak the cells of a given host to varying degrees, Boothroyd said. "We hypothesize that, depending on which version of the ROP16 gene a given strain carries and which host is infected, it may carry out this task with greater or lesser efficiency," he said. "As a result, when a strain infects that host, the 'tweaking' is just right and the host is successfully infected with the minimum of damage."

Yet in a different host infected by that same strain, the activity of the ROP16 protein may be too strong, causing the parasite infection to rapidly overwhelm and kill the host. Alternatively, that version of ROP16 may not work in a given host at all, causing an excessive immune response in the host.

"Obviously the organism needs some powerful tools to manipulate the host's immune system to ensure its survival," said Saeij. "So it is very well possible that each time Toxo encountered new hosts, it expanded its arsenal of tools (duplicating or evolving existing kinases) to deal with the new challenges."

Mitzi Baker | EurekAlert!
Further information:
http://mednews.stanford.edu

Further reports about: Boothroyd Kinase ROP16 Toxoplasma parasite

More articles from Life Sciences:

nachricht Bioenergy cropland expansion could be as bad for biodiversity as climate change
11.12.2018 | Senckenberg Forschungsinstitut und Naturmuseen

nachricht How glial cells develop in the brain from neural precursor cells
11.12.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Electronic evidence of non-Fermi liquid behaviors in an iron-based superconductor

11.12.2018 | Physics and Astronomy

Topological material switched off and on for the first time

11.12.2018 | Materials Sciences

NIST's antenna evaluation method could help boost 5G network capacity and cut costs

11.12.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>