Artemisinin combination therapies (ACTs) have greatly decreased deaths caused by Plasmodium falciparum malaria, a mosquito-borne disease that accounts for roughly 90 percent of the world’s malaria mortality.

But Plasmodium falciparum is becoming increasingly resistant to ACTs, making an already dangerous parasite even more threatening.

“Like antibiotic drugs used to treat other microbial infections, antimalarial drugs put evolutionary pressure on the parasite to evolve or to go extinct,” explained Dr. Justin Gibbons, a post-doctoral scholar in the USF College of Public Health’s (COPH) Center for Global Health and Inter-Disciplinary Research. “Random genetic changes occur all the time in these parasites and some of these changes may confer resistance to the drug treatment. The greater the resistance, the more likely these altered parasites can successfully reproduce, and, over time, parasites can become more and more resistant to ACTs until they won’t work anymore.”

Gibbons and his fellow researchers, including those from USF’s Morsani College of Medicine and the University of Glasgow, have identified a mutation in the MRST gene in Plasmodium falciparum that increases its sensitivity to ACT.

Their study, “A novel Modulator of Ring Stage Translation (MRST) gene alters artemisinin sensitivity in Plasmodium falciparum,” was published in the journal mSphere in May. The first author of the study was Caroline Simmons, who recently graduated the COPH with her PhD.

“Most studies of ACT resistance mechanisms identify broad pathways that are changed, but not the contribution of specific genes,” Gibbons said. “This study identified and characterized a gene that regulates pathways relevant to ACT resistance mechanisms that had not been identified before.”

According to Gibbons, Plasmodium falciparum resists artemisinin treatment by entering a dormant state until the drug has been cleared by the body—and then resumes growth.

“Instead of entering a quiescent state that is artemisinin resistant, the mutant is more sensitive to artemisinin, suggesting the decreased translation during this period is hobbling the normal artemisinin response,” Gibbons said.

Identifying this mutant gene can be a boon to those treating ACT-resistant Plasmodium falciparum.

“This gene can potentially be targeted by drugs that will impair the parasite’s ability to respond to artemisinin,” Gibbons noted, “which could extend the useful life of ACT.”

Story by Donna Campisano, USF College of Public Health