Metabolomic parasite profile aids in fighting malaria

Using a technique based on mass spectrometry and developed by Princeton chemistry professor Joshua Rabinowitz, the researchers developed a new “metabolomic” profile of the malaria parasite that allowed them to study its chemical processes and enzymes. This profile showed that the parasite removes or consumes large quantities of arginine, said biology professor Manuel Llinas, who co-authored a Feb. 18 paper from the collaboration that appeared in the scientific journal Cell Host & Microbe.

Arginine plays a crucial role in the human immune system, Llinas noted, explaining that when the parasite consumes arginine, it weakens the host body’s immune response and leaves the host vulnerable to more severe forms of malaria.

“The parasite thrives because it’s able to reduce the arginine that’s in the host,” Llinas said. “This is important because it suggests that this process of getting rid of arginine is favoring the parasite’s survival in humans.”

This discovery may be used to someday provide individuals at risk for contracting malaria with arginine supplements, Llinas added. Since the parasite depletes the body’s natural supply of arginine, providing more of the chemical might bolster the immune system enough to protect against the most serious stages of malaria, Llinas explained, noting that this is especially important because currently there is no vaccine to fight off the infectious disease.

Past studies had shown that arginine supplements can reduce malaria rates, Llinas said, but those results have not been used to improve treatment because they were not well understood.

“There was never any evidence that [providing supplementary arginine] was actually a direct way of getting back to the parasite until now,” Llinas explained.

Llinas said that he hopes this discovery is only the first of several things that his research team will learn from the metabolomic profile. The initial aim of the research was to identify the metabolic processes and enzymes of the parasite that could be targeted by future anti-malarial drugs, he added.

“We’ve catalogued what the metabolism of the parasite looks like, which hasn’t been done before at this level because the technology hasn’t been available,” Llinas said.

He explained that his group is now looking for new compounds that the parasite produces and, in particular, compounds that are unique to the parasite and don’t exist in the human hosts. These parasite-specific compounds, he added, could be then targeted with drugs that would attack the infectious disease without harming the human body.

Developing new drugs to combat malaria is an ongoing challenge for researchers and pharmaceutical companies because the parasite develops resistances to common medicines very quickly. According to the website of the Centers for Disease Control, between 350 million and 500 million people worldwide are infected with malaria each year, and at least one million of them die annually.

Llinas co-authored the paper with Rabinowitz, Kellen Olszewski GS, University research specialist Daniel Wilinski and three members of Drexel’s Center for Molecular Parasitology: James Burns, Joanne Morrisey and Akhil Vaidya.