According to the World Health Organization (WHO), nearly half of the world’s population in 2021 was at risk of malaria, a life-threatening disease most often transmitted to humans via mosquito bites. And while the disease is most prevalent in tropical countries, several cases of locally acquired malaria have recently been reported in the U.S.

While there are treatments for malaria, the main drug, artemisinin, is becoming less and less effective against a particularly deadly malaria-causing parasite called Plasmodium falciparum.

To better understand this drug resistance, a group of researchers, including those from the USF College of Public Health (COPH), set out to examine the genetic changes that occur in parasites treated with antimalarial drugs.

Their research, “Chemogenomic Profiling of a Plasmodium falciparum Transposon Mutant Library Reveals Shared Effects of Dihydroartemisinin and Bortezomib on Lipid Metabolism and Exported Proteins,” was published in June in the journal Microbiology Spectrum.

“Artemisinin works by causing damage to the parasite through a process involving a substance called heme, which is released when the parasite digests hemoglobin,” explained lead author Camilla Valente Pires, a postdoctoral scholar at the COPH’s Center for Global Health and Inter-Disciplinary Research who works in the lab of Dr. John Adams.  Adams is a malaria expert and a co-author of the paper. “However, the specific genetic changes that lead to resistance to artemisinin are complex and not yet fully understood,” Pires added. “That’s why, in this study, we took a systematic approach to study the genes responsible for how the malaria parasite responds to the oxidative stress caused by antimalarial drugs.”

The researchers, who, in addition to the team from the COPH, included scientists from USF’s Morsani College of Medicine, the University of Notre Dame, the University of Glasgow and the University of Cambridge, tested a group of genetically modified malaria parasites using a drug called dihydroartemisinin (DHA), which is similar to artemisinin, and another drug called bortezomib (BTZ), which blocks a specific process in the parasite. This allowed the scientists to create profiles of how the genes in the parasites interacted with the drugs. 

By comparing the response of the genetically modified parasites to the drugs, the researchers said they could better understand the parasite’s response—or lack of it—to artemisinin.

“We found that lipid metabolism and the export of proteins played important roles in how the parasites reacted to the drugs,” Pires said. “Surprisingly, we discovered that specific factors involved in protein export were significant differences between how DHA and BTZ worked.”

Pires said that by understanding these factors, scientists can gain insights into how the drugs work and how the parasite interacts with them.

“In the future, additional studies can build upon our findings and confirm the specific ways in which these factors interact,” Pires stated. “This will help us deepen our understanding of how the parasite responds to artemisinin and aid in the development of effective combinations of drugs for treating malaria.”

Story by Donna Campisano, USF College of Public Health