Researchers from St George’s, University of London (UK) and the Instituto de Medicina Molecular (Lisbon, Portugal) have discovered how iron is controlled by the malaria parasite within the human body, providing the first in-detail characterization of an important iron transport pathway.
Malaria kills around 600,000 people annually by World Health Organization estimates, with this figure expected to sharply rise as drug resistance increases. Henry Staines, a senior research fellow at St George’s, University of London, explained that iron is critical to the malaria parasite’s survival in the human body, but can also be toxic at high levels. Iron is critical, he continued, to the effectiveness of antimalarial drugs such as artemisinins and chloroquine.
“This research will not only allow us to identify new ways to attack the parasite but will help us to understand how our current arsenal of antimalarial drugs work,” Staines posited. “This is important because antimalarial drugs such as artemisinin-based combination therapies are not as effective as they were in South East Asia, which is a worrying trend.”
The team utilized a mutated form of baker’s yeast, in which the sequence for a specific iron transport protein had been removed from the yeast’s DNA. Staines explained: “With the yeast mutant unable to make this iron transport protein, it loses the ability to grow where iron is present. We thought a protein from the malaria parasite might perform the same iron transporting role, as the one lacking in the mutant yeast.”
Ksenija Slavic from the Instituto de Medicina Molecular added that to confirm their hypothesis, the team introduced a specific DNA sequence from the malaria parasite into the mutant yeast, and showed that the inclusion caused the yeast to regain their ability to grow in the presence of iron. She continued, “A mutant malaria parasite was also created by removing the iron transporter’s gene, which resulted in reduced numbers of parasites in the liver, where they first multiply, and subsequently in the blood, at which point patients become ill.”
One of the senior authors of the study, Maria Mota, elaborated: “Inside red blood cells, we found that these mutant parasites contained an increased amount of iron that could be potentially toxic, explaining the reduced numbers. Both findings imply that the gene helps the parasite to tolerate iron.” She concluded, “This greater understanding of iron regulation in the malaria parasite could lead to urgently needed new treatment strategies.”
The researchers plan to next investigate how the mutant parasites are impacted by iron-utilizing anti-malarial drugs.