International team of researchers identify new drug targets, resistance genes in malaria

Through genome analysis and chemogenetics, researchers at the University of California (UC) San Diego School of Medicine, along with national and international associates, have confirmed genetic modifications that have led to malaria’s drug resistance and revealed new drug targets contained within the parasites’ biology.

At the core of the study are 262 parasite cell lines. Those lines are part of Plasmodium falciparum–the pathogens that actually cause malaria. In those hundreds of cell lines, scientists found resistance to 37 different antimalarial compounds.

“A single human infection can result in a person containing upwards of a trillion asexual blood stage parasites,” Elizabeth Winzeler, a professor at UC San Diego School of Medicine and senior author of the study, said. “Even with a relatively slow random mutation rate, these numbers confer extraordinary adaptability. In just a few cycles of replication, the P. falciparum genome can acquire a random genetic change that may render at least one parasite resistant to the activity of a drug or human-encoded antibody.”

By studying the genome, scientists like Winzeler are able to better guide new drug discovery efforts. That genome, however, is particularly adept at altering itself to dodge and fight off both drug treatment and the natural human immune system. That, in part, is what has led to malaria’s high toll on humanity. The World Health Organization reported 445,000 deaths resulting from the parasite in 2016, as well as 216 million cases worldwide.

The results of this study were published in the Jan. 12 issue of Science.