Malaria, a disease that kills over 600,000 people annually, faces increasing drug resistance, necessitating the exploration of new therapeutic targets. Researchers at the University of Utah Health have identified a protein, DMT1, crucial for iron utilization in malaria parasites, presenting a promising avenue for novel antimalarial drug development. The study, published in PNAS, suggests that inhibiting DMT1 could effectively combat malaria by disrupting the parasite's iron acquisition.
The Role of DMT1 in Malaria Parasites
Iron is essential for the survival and proliferation of malaria parasites within human red blood cells. These parasites must extract iron from hemoglobin, a process that has remained largely mysterious. According to Paul Sigala, PhD, associate professor of biochemistry at the University of Utah, "We still don't really understand how parasites acquire iron in the red blood cell." The research team focused on DMT1 due to its similarity to metal transport genes in other organisms.
Experimental Evidence
To investigate DMT1's role, researchers used genome editing to control DMT1 production in malaria parasites. When DMT1 production was turned off, the parasites died rapidly, unable to infect more blood cells. This rapid demise, as noted by Sigala, indicates that blocking DMT1 impairs nearly all aspects of parasite viability during blood-stage infection. Further experiments demonstrated that reducing DMT1 activity slowed parasite growth, but this could be reversed by increasing iron availability. This confirms that DMT1 is specifically involved in iron transport.
Therapeutic Potential
The researchers are optimistic about DMT1 as a drug target. Kade Loveridge, a graduate researcher in biochemistry, noted that DMT1's moderate similarity to human iron transporters allows for the design of parasite-specific inhibitors. The rapid death of parasites when DMT1 is inhibited suggests that drugs targeting this protein could be faster-acting than current antimalarial options. The lab is currently testing existing iron transport inhibitors for their potential as antimalarial drugs.
Loveridge added, "We're kind of cracking the door. I hope that other people can throw it wide open," emphasizing the potential for future research to build upon this discovery and develop more effective antimalarial strategies.
