Researchers have identified a "key metabolic enzyme" the malaria parasite requires at each stage of infection; learning how to target this enzyme could be a huge step towards fighting the infection.
"Perhaps the most exciting aspect of our findings is that this enzyme is required at all stages of the parasites' life cycle in humans," co-first author Marcus C.S. Lee, PhD, associate research scientist in microbiology & immunology at CUMC, said in a Columbia University Medical Center news release. "This is important because most antimalarials are effective at killing the parasites only as they circulate in the bloodstream. However, the parasites can hide in the liver for years before reemerging and triggering a relapse of the disease. By identifying this enzyme, we may be able to develop a new way to kill the parasites in their dormant stage."
The team analyzed over a million drug compounds against the deadly parasite and was able to pinpoint the enzyme, dubbed phosphatidylinositol 4-kinase (PI4K). The noticed a class of drug compounds called imidazopyrazines was able to kill of many of the Plasmodium falciparum parasite strains. These compounds were also found to have no negative side effects on human cells.
"The researchers identified the target of the imidazopyrazines by evolving parasite cell lines that were resistant against the drugs and then analyzing the parasites' genomes for the changes responsible for conferring resistance. Those genetic changes pointed to the gene that encodes PI4K," the news release reported.
The team used "novel genetic tools" to make their finding. They found the compound inhibited the function of the parasite's Golgi ("the organelle that packages proteins for delivery to other cellular destinations").
"We think that disrupting the function of PI4K at the Golgi stops the parasite from making new membranes around its daughter cells, thereby preventing the organism from reproducing," Dr. Lee said.
