Video SNiP—In Mice, A Single Mutation Topples Malaria’s Defenses

Plasmodium falciparum—the microscopic parasite that causes malaria—is a “master hider,” says Susan Pierce, Ph.D., chief of NIAID’s Laboratory of Immunogenetics. Somewhere in its genome of more than 5,400 genes are instructions for biological machinery that can help this protozoan pest elude the human immune system for years after infection. In fact, a child in Africa may acquire life-threatening malaria dozens of times from infected mosquitoes before she finally mounts a protective immune response in adolescence.

In a new NIAID Video SNiP, researchers explain their efforts to track down the genetic source of Plasmodium’s stealth. Their findings were published online today in Science Advances.

Dr. Pierce, along with colleagues Louis Miller, M.D., chief of the Malaria Cell Biology Section in NIAID’s Laboratory of Malaria & Vector Research, and research fellow Munir Akkaya, M.D., D.Phil., explored transcription factors—proteins that regulate the activity of other genes—in Plasmodium’s genome with international collaborators. By altering a single nucleotide in a gene that codes for one transcription factor, researchers found that Plasmodium was much less able to escape the immune systems of mouse models. While unaltered Plasmodium went on to establish malaria in mice, the mutant parasites were easily bested when the mouse immune system produced protective antibodies and inflammatory proteins called cytokines.

Because this transcription factor regulates the activity of 46 different genes, any number of those genes may play a role in making Plasmodium more visible to the immune system. Researchers suggest that further exploring these genes may help elucidate a target for experimental therapeutics or even a preventative vaccine against malaria.

Watch the video SNiP:

Reference:

M. Akkaya et al. A single nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor alters the development of host immunity.  Science Advances DOI: 10.1126/sciadv.aaw6957 (2020)