A new discovery about the malaria-related parasite Toxoplasma gondii -- which can threaten babies, AIDS patients, the elderly and others with weakened immune function -- may help solve the mystery of how this single-celled parasite establishes life-long infections in people.
The study, led by a University of South Florida research team, places the blame squarely on a family of proteins, known as AP2 factors, which evolved from the regulators of flowering in plants.
In findings published today in the Proceedings of the National Academy of Sciences, the researchers demonstrate AP2 factors are instrumental in flipping a developmental "switch" that transitions the parasite from a rapidly dividing form destructive to healthy tissue to a chronic stage invisible to the immune system. They identified one factor, AP2IX-9, that appears to restrict development of Toxoplasma cysts that settle quietly in various tissues, most commonly the host's brain.
A better understanding of how the switch mechanism works may eventually lead to ways to block chronic Toxoplasma infections, said study principal investigator Michael White, PhD, professor of global health and molecular medicine at USF Health and a member of the Center of Drug Discovery and Innovation, a Florida Center of Excellence at USF.
White and his colleagues are among the world's leading experts in T. gondii, combining approaches from biochemistry, genetics and structural biology to look for new ways to combat the parasitic disease toxoplasmosis.
No drugs or vaccines currently exist to treat or prevent the chronic stage of the disease. The T. gondii parasites may remain invisible to the immune system for years and then reactivate when immunity wanes, boosting the risk for recurrent disease.
"The evolutionary story of Toxoplasma is fascinating," White said. "We were blown away to find that the AP2 factors controlling how a flower develops and how plants respond to poor soil and water conditions have been adapted to work within an intracellular human parasite."
Ages ago the ancestors of malaria parasites genetically merged with an ancestor of plants, and the primitive plant donated its AP2 factors to the future malaria family.
"Our study showed that, like the AP2 factors help a plant survive a stressful environment, the AP2 factors of T. gondii help the parasite decide when the time is right to grow or when to form a tissue cyst that may lie dormant in people for many years," White said.
Toxoplasmosis, the infection caused T. gondii, is commonly associated with the medical advice that pregnant women should avoid contact with litter boxes. That's because infected cats play a big role in spreading the disease. The tiny organism thrives in the guts of cats, producing countless egg-like cells that are passed along in the feces and can live in warm moist soil or water for months.
People can acquire toxoplasmosis several ways, usually by exposure to the feces of cats or other infected animals, by eating undercooked meat of infected animals, or drinking water contaminated with T. gondii.
Up to 30 percent of the world's population is estimated to be infected with the T. gondii parasite. In some parts of the world, including places where sanitation is poor and eating raw or undercooked meat is customary, nearly 100 percent of people carry the parasite, White said.
Few experience flu-like symptoms because the immune system usually prevents the parasite from causing illness, but for those who are immune deficient the consequences can be severe.
The disease may be deadly in AIDS patients, organ transplant recipients, patients receiving certain types of chemotherapy, and infants born to mothers infected with the parasite during or shortly before pregnancy. Recently, toxoplasmosis has been linked to mental illness, such as schizophrenia and other diseases of dementia, and changes in behavior.
Because it is common, complex and not easily killed with standard disinfection measures, the toxoplasma parasite is a potential weapon for bioterrorists, White added.
The USF-led study was supported by grants from the National Institutes of Health. White's team worked with researchers at Princeton University, Albert Einstein College of Medicine, and Indiana University School of Medicine. Joshua Radke, a PhD student in the USF Health Department of Molecular Medicine, was a first author of the study.
Article citation: "ApiAP2 transciption factor restricts development of the Toxoplasma tissue cyst;" Joshua B. Radke, Oliver Lucas, Erandi K. DeSilva, YanFen Ma, William J. Sullivan, Jr., Louis M. Weiss, Manuel Llinas, and Michael W. White; Proceedings of the National Academy of Sciences; http://www.pnas.org/cgi/doi/10.1073/pnas.1300059110
USF Health's mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician's Group. The University of South Florida is a global research university ranked 50th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities. For more information, visit http://www.health.usf.edu
Anne DeLotto Baier | EurekAlert!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy