An international team of researchers has identified a potential new strategy for treating toxoplasmosis—the infection caused by the parasite Toxoplasma gondii, which commonly infects cats but can also spread to humans.
Humans typically contract the parasite through close contact with infected cats or by consuming undercooked, contaminated meat. Once inside the body, the organism travels through the digestive system, enters the bloodstream, and eventually reaches the brain. There, it forms microscopic cysts, entering a dormant state in which it can persist for the lifetime of its host.
Toxoplasma infection is extremely widespread. Serological studies suggest that roughly 30–50 percent of the global population has been exposed, with prevalence varying significantly between regions—often higher in developed countries.
For most people, infection produces no obvious symptoms. However, some research has linked chronic toxoplasmosis to subtle behavioral and personality changes. Other studies have explored associations with neurological conditions, including schizophrenia and bipolar disorder, though these links remain an area of ongoing investigation.
Certain groups face higher risks. Pregnant women are particularly vulnerable because the parasite can harm fetal development, which is why they are advised to avoid handling cat litter. Individuals with compromised immune systems also face severe danger, as toxoplasmosis can become life-threatening in such cases.
At present, no treatment can fully eliminate the dormant cyst stage of the parasite. One reason is that scientists have had a limited understanding of the biological mechanisms that allow T. gondii to survive long-term in the brain.
New findings, however, may change that outlook. Researchers at the University of Michigan discovered that once inside the brain, the parasite enters a low-metabolism “hibernation” state and relies on a specific enzyme to survive.
This enzyme—cathepsin protease—enables the parasite to break down and recycle cellular material, providing energy during dormancy. When scientists inhibited the enzyme, both genetically and with drug compounds, the parasites died.
“These findings suggest an unanticipated function for parasite lysosomal degradation in chronic infection and identify an intrinsic role for autophagy in the T. gondii parasite and its close relatives.
This work also identifies a key element of Toxoplasma persistence and suggests that VAC proteolysis is a prospective target for pharmacological development.”
— The researchers write.
While promising, the breakthrough remains at an early stage. So far, the enzyme has only been successfully inhibited in laboratory (in vitro) settings. The compounds used cannot cross the blood–brain barrier, meaning they cannot yet reach the dormant parasites inside a living host.
Future work will focus on developing similar molecules—or delivery systems—capable of penetrating the brain to target and eliminate the cysts.
Reference:
Manlio Di Cristina et al. (2017). Toxoplasma depends on lysosomal consumption of autophagosomes for persistent infection. Nature Microbiology. DOI: 10.1038/nmicrobiol.2017.96.