Scientists at the University of California, Riverside have found that Toxoplasma gondii, a parasite infecting up to one-third of the world's population, is more active in the brain than previously thought. Their study shows cysts contain multiple subtypes of the parasite, some primed for reactivation and disease. This discovery could guide new treatments for a lifelong infection that resists current drugs.
Toxoplasma gondii spreads through undercooked meat or contact with contaminated soil and cat feces, forming microscopic cysts in the brain and muscles that persist for life. In healthy people, these cysts often cause no symptoms, but they can reactivate in those with weakened immune systems, leading to severe issues like toxoplasmic encephalitis or vision loss from retinal toxoplasmosis. Pregnant women face particular risks, as the infection can harm developing fetuses with immature defenses.
For decades, researchers viewed cysts as simple dormitories for a single parasite type, the bradyzoite. However, using single-cell RNA sequencing on parasites extracted from mouse brains—a natural host for the parasite—the UC Riverside team uncovered a more dynamic picture. Each cyst, up to 80 microns wide and packed with hundreds of bradyzoites about five microns long, houses at least five distinct subtypes. These vary in function, with some focused on survival, others on spread, and certain ones ready to convert into fast-multiplying tachyzoites that trigger illness.
"We found the cyst is not just a quiet hiding place—it's an active hub with different parasite types geared toward survival, spread, or reactivation," said Emma Wilson, a professor of biomedical sciences and lead author. The study, published in Nature Communications, challenges the traditional linear life cycle model of the parasite. Past research struggled with cysts due to their slow growth and embedding in tissues like neurons, skeletal muscle, and cardiac muscle, but this work used enzymatic digestion of cysts from infected mice to analyze them directly.
Current treatments control acute infections but fail against cysts, explaining persistent challenges in eradication. "By identifying different parasite subtypes inside cysts, our study pinpoints which ones are most likely to reactivate and cause damage," Wilson noted. This could target therapies more precisely, especially for congenital toxoplasmosis. The findings, funded by the National Institute of Allergy and Infectious Diseases, involved co-authors Arzu Ulu, Sandeep Srivastava, Nala Kachour, Brandon H. Le, and Michael W. White.
