Epigenetic Study Reveals Potential Achilles’ Heel in Malaria Parasite
Scientists at the University of California, Riverside report finding a potential biological weakness in the Plasmodium parasite responsible for causing malaria. They say they discovered low levels of DNA methylation in Plasmodium’s genome “that may be critical to the survival of the parasite,” according to Karine Le Roch, Ph.D., an associate professor of cell biology, who added that the parasite is showing resistance to artemisinin, the main drug used to treat the disease.
The research team published their paper ("Genome-wide Mapping of the DNA Methylation in the Human Malaria Parasite") appears in the December issue of Cell Host & Microbe.
DNA methylation is a biochemical process involving the modification of DNA that plays an important role in development and disease. It regulates a number of processes including gene expression and stress responses.
“We performed a genome-wide analysis of DNA methylation in the human malaria parasite Plasmodium falciparum. We mapped the positions of methylated cytosines and identified a single functional DNA methyltransferase (Plasmodium falciparum DNA methyltransferase) that may mediate these genomic modifications,” wrote the investigators. “These analyses revealed that the malaria genome is asymmetrically methylated and shares common features with undifferentiated plant and mammalian cells. Notably, core promoters are hypomethylated, and transcript levels correlate with intraexonic methylation. Additionally, there are sharp methylation transitions at nucleosome and exon-intron boundaries. These data suggest that DNA methylation could regulate virulence gene expression and transcription elongation.”
Until now, the existence of DNA methylation in the Plasmodium parasite was disputable, Dr. Le Roch said. There were published contradicting studies that used old technology to search for methylation, but Dr. Le Roch's team was able to confirm low levels of methylation using classical molecular approaches as well as new sequencing technology.
The DNA methylation enzyme found in Plasmodium is also quite different than the one in humans, continued Dr. Le Roch, “and because it is different we can eventually find a way to target it and shut it down. If a drug can be developed that specifically inhibits the methylation enzyme, it could kill the parasite in infected humans.”