Research led by a team of investigators at the Indiana University School of Medicine has detailed the discovery of a new protein and other proteins it connects with, which they say could lead to the development of new drugs that control toxoplasma gondii – the parasite that causes toxoplasmosis.
The researchers say their findings, published in the journal PLOS Pathogens, may also lead to new research avenues for the treatment of malaria.
According to the Centers for Disease Control and Prevention (CDC), toxoplasmosis is believed to be the
Transmission of the parasite can occur through eating undercooked or contaminated meat from infected livestock, eating meat that was prepared with contaminated utensils, or handling infected meat and not washing hands thoroughly.
Cats are also a main cause of the spread of toxoplasma. The parasite is found in their feces, and can be transmitted to humans if they come into contact with it, through cleaning a litter tray for example.
Over 60 million Americans are carriers of the toxoplasma parasite, but the CDC note that since the human immune system is usually able to prevent the parasite from causing illness, very few people experience symptoms from it.
However, people with compromised immune systems and women who are pregnant are more likely to suffer illness from the parasite.
Through their research, the investigators discovered an enzyme called GCN5b. They found that this protein is crucial for the toxoplasma parasite to duplicate, meaning that if the protein is inhibited, it could be controlled.
Further investigation revealed that GCN5b plays a part in the mechanisms responsible for switching genes on or off (gene expression) in the parasite, and that the protein interacts with other enzymes that were found to be more “plant-like” than their human counterparts.
In detail, the researchers say that the plant-like transcription factors found in GCN5b – proteins that attach themselves to DNA – cause the GCN5b complex to switch an array of genes on or off.
When the team deactivated the GCN5b complex, they found that this stopped toxoplasma replication.
Explaining the importance of these findings, Prof. William J. Sullivan Jr, associate professor of pharmacology and toxicology at the Indiana University School of Medicine, says:
“GCN5b is a very different protein than its human counterpart, and proteins it interacts with are not found in humans.
That’s what makes this exciting – rather than just having one enzyme that we could go after, there could be a whole collection of associated enzyme components that could be potentially targeted for drug therapies to control this parasite.”
Dr. Sullivan notes that because the GCN5b protein is active in both undeveloped and severe forms of toxoplasmosis, the enzyme and those it interacts with may be potential drug targets for treatment of the condition.
He adds that because the transcription factors found in the protein are plant-like and not found in humans, drug targeting would be significantly less likely to affect human proteins and cause negative outcomes.
Furthermore, the investigators say their findings could lead to the development of new drugs that treat malaria, since researchers use toxoplasma as a model organism for plasmodium – the malaria parasite.
Dr. Sullivan explains that plasmodium also has a GCN5 enzyme and plant-like proteins.
Medical News Today recently reported on a study, also published in PLOS Pathogens, detailing the discovery of clues as to why toxoplasma can cause blindness in some people but not in others.