By Bunmi Yekini
In a breakthrough that could pave the way for new, resistance-proof malaria treatments, scientists from the Francis Crick Institute and the Gulbenkian Institute for Molecular Medicine (GIMM) have identified a family of proteins essential for the malaria parasite’s ability to infect humans.
The study, published today in Nature Microbiology, focuses on a group of proteins called FIKK kinases, which are exported by Plasmodium falciparum, the deadliest malaria parasite. These proteins allow the parasite to remodel red blood cells, a process that causes the infected cells to stick together and form dangerous clots.
“About 1 million years ago, Plasmodium crossed from birds into great apes,” said Dr. Moritz Treeck, head of the Cell Biology of Host-Pathogen Interaction Laboratory, now based at GIMM. “With this cross, the FIKK kinase family expanded to enable infection of our closest relatives. A relatively short time ago, Plasmodium falciparum crossed from great apes to humans, and we’ve shown that the kinases needed for survival in great apes are still required for survival in humans.”
The researchers analyzed over 2,000 P. falciparum samples and found that 18 of the 21 FIKK kinases were highly conserved—suggesting they are critical for human infection. Experiments showed that these kinases target different proteins within the host cell, with one even modifying tyrosine, an amino acid not previously known to be targeted by parasites.
The team also collaborated with GlaxoSmithKline (GSK) to screen known human kinase inhibitors, identifying three promising compounds—two of which were able to block most FIKK kinases in test-tube experiments.
“This project has been very collaborative across multiple institutions and disciplines,” said Dr. Hugo Belda, co-first author and postdoctoral researcher at GIMM. “Current drugs mostly target single proteins, which makes the emergence of drug resistance more likely. Developing compounds which target several proteins at once, like those blocking all FIKK kinases, may be one way to tackle this problem.”
The next step, researchers say, is to develop these compounds further into drugs that can be safely used in humans.
Malaria continues to infect over 200 million people and claim more than 500,000 lives each year. As resistance to existing treatments grows, this discovery offers a potential new direction in the global fight against the disease.