Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A parasite’s exit strategy: Researchers discover protein necessary for spread of common infection

27.01.2009
Study could lead to development of new drugs, vaccine

University of Michigan researchers have discovered that a common parasite infecting one in five Americans needs an escape hatch to go on a destructive mission that can damage the brain, eyes and other organs.

The protozoan parasite called Toxoplasma gondii infects up to 23 percent of Americans. In some areas of the world, up to 95 percent of the population serves as host to this parasite, which causes toxoplasmosis, a serious infection that can lead to birth defects, eye disease and life-threatening encephalitis.

In the study published in the current issue of Science, UM researchers report the protein called TgPLP1 is responsible for helping the parasite spread infection. This research breakthrough may one day aid in developing drugs or vaccines to treat or prevent toxoplasmosis or related diseases, including malaria.

“For some time we've been interested in how this parasite successfully enters cells,” says Vern B. Carruthers, Ph.D., the study’s senior author and associate professor in the Department of Microbiology and Immunology at the U-M Medical School.

“A couple of years ago, we identified several new proteins secreted by the parasite. Among these was TgPLP1, which captured our interest because it is related to proteins of our own immune system responsible for warding off infection and cancer," Carruthers says.

After the initial period of infection, which may cause mild flu-like symptoms, Toxoplasma gondii goes on to lie dormant in a person's brain and central nervous system. But if a person's immune system becomes compromised, such as from human immunodeficiency virus (HIV) infection or organ transplant surgery, the Toxoplasma infection can be reactivated.

In an immunocompromised person, Toxoplasma gondii amplifies the infection by invading a cell and undergoing several rounds of replication within that cell. "Then it has to escape from the cell in order to find and infect additional cells," Carruthers explains.

TgPLP1 is a type of protein responsible for forming pores, or small openings, in the cell membrane to allow the parasite to escape and cause disease more rapidly throughout the host.

Research details

Carruthers' research team pinpointed how TgPLP1 works by generating and observing a cultured parasite that does not have the TgPLP1 protein. While observing the movements of the mutant parasite with video microscopy, the team noticed that, compared to the normal parasite, the parasite without TgPLP1 struggled to get out of the host cells and remained trapped within the cell membrane.

The research team offers several theories as to how the protein enhances the parasite's ability to cause disease.

“We think that this protein helps the parasite escape by weakening the membranes that encase the parasite during replication,” says Bjorn F.C. Kafsack, Ph.D., a research fellow in U-M’s Department of Microbiology and Immunology and the study’s first author. “It’s also possible that TgPLP1 works by allowing other proteins to break out ahead of the parasite. These other proteins could digest components of the host cell that serve as barriers to the parasite getting out of the host cell.”

Even when infected host cells were treated with a drug that would normally trigger the parasite to leave, TgPLP1-deficient parasites had difficulty or failed to exit from the host cell.

For the next stage of the research, the team injected mice with the TgPLP1-deficient parasites. "The mutant parasites grow quite quickly when we culture them in the lab but when we infect mice with them, they're severely weakened," a fact that came as a surprise, Kafsack says.

Significantly more TgPLP1-deficient parasites were needed to cause disease in the mice, compared to the normal parasites, researchers found.

“It implies that the ability of the parasite to quickly escape from its old host cell is a critical step during infection of animals,” Kafsack says.

Implications

Now that researchers know the purpose and importance of this protein for the disease, they may find ways of interfering with its functions, such as finding a selective treatment that disables the parasite protein and therefore slows or stops Toxoplasma gondii's spread.

Using the gene-deleted mutants developed in this research against Toxoplasma gondii, scientists may eventually be able to develop a vaccine against this common infection, Carruthers says.

"Because the gene deletion mutants are so weakened, they could be used as a vaccine strain to initiate an immune response that may be protective, but without persisting or causing disease as the normal parasites would," Carruthers says.

This research may also offer insights into how the parasite that causes malaria, which kills more than 1 million people each year, might spread and cause infection.

"Because the malaria parasite has proteins similar to the one in the study, it may also use a pore-forming protein to escape from infected red blood cells," Carruthers says. Better understanding these mechanisms may someday help researchers develop new strategies for controlling the spread of the disease.

Funding for the research came from the National Institutes of Health and the American Heart Association.

Citation: Science, Vol. 323, No. 5913, pp. 530-533.

Written by Kim Roth

Shantell M. Kirkendoll | University of Michigan
Further information:
http://www.umich.edu

More articles from Studies and Analyses:

nachricht Real-time feedback helps save energy and water
08.02.2017 | Otto-Friedrich-Universität Bamberg

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>