Brain parasite

Parasite; A team of researchers has found that a dangerous type of parasite that affects the brain; but maintains a stable supply of essential nutrients as it replicates in the host cell. In an unexpected turn of events, the body itself delivers food to the harmful predator. The researchers from Indiana University School of Medicine found that Toxoplasma gondii,a single-celled parasite that can infect animals, including humans, invades the host’s cells, requiring a lot of resources. The parasite gets most of the nutrients intended for the cell, rapidly depleting host nutrient supply.

Toxoplasma gondii, the causative agent of Toxoplasmosis, is one of the most common parasitic infections worldwide. The Centers for Disease Control and Prevention (CDC); but reports that approximately 11% of the population, 6 years old and above, have been infected with the parasite. Moreover, more than 60% of some populations across the globe acquired the infection at some point in their lives. Most of the cases occur in locations that have humid and hot climates, and lower altitudes, providing an environment conducive for oocyte survival.

Rapid depletion of essential nutrients in host cells

This new study shows that the parasite is auxotrophic for many nutrients such as tryptophan, arginine, and purines. This means that the organism has an additional nutritional growth requirement, and it gets the nutrients from the host. Due to the higher demand for nutrients in the host cells due to the invasion of the parasites, rapid depletion of essential nutrients alerts the body. The body, in turn, stimulates bodily processes to compensate with the depleted nutrient supply.

Activation of the integrated stress response

The researchers led by Leo Augusto, a postdoctoral fellow, in collaboration with Ronald Wek; a molecular biology professor, and Bill Sullivan, a microbiology professor; found that cellular starvation of essential nutrients triggers a stress response; but known as the integrated stress response (ISR), that occurs in the first two hours of parasite infection.

Nutrient starvation stimulates the integrated stress response (ISR) through the process of phosphorylation; but that involves an essential translation factor, eIF2 (eukaryotic translation initiation factor). As a result, this decreases global protein synthesis parallel to the preferential translation of gene transcripts linked to stress adaptation; but including encoding the transcription factor ATF4 (CREB2). This triggers genes that control amino acid metabolism.

Host cells sense their nutrients being depleted

The researchers used many mutant host cells to determine that GCN2, a type of protein, becomes stimulated and activated as the parasites proliferate and consume the cell’s arginine supply. As the cell’s supply decreases, they mapped what happened after the activation of the protein. They discovered that the host cells invaded by Toxoplasma gondii produce more CAT1, an arginine transporter, on the cell’s surface.

As a result, the body senses the depleted arginine supply. The arginine transporter attracts more arginine, hence, the parasite continues to consume the nutrients it needs to survive. The study findings suggest that host cells have the ability to feel when their nutrients are not enough for their needs. Unaware of the parasites invading then, they try to provide more arginine supply to make up for the depleted supply.