Elusive protein protects malaria parasite from heme

Hemozoin crystals in the food vacuole of the malaria parasite. Color was added to this micrograph using Adobe Photoshop. Click here for more information.

Blacksburg, Va. – Researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech have identified Heme Detoxification Protein (HDP), a unique protein encoded in the malaria genome that represents a potential target for developing new malaria drugs. The team, which includes researchers at Washington University School of Medicine, the United States National Institutes of Health, the United States Food and Drug Administration as well as other researchers at Virginia Tech, has characterized HDP and demonstrated that it plays a major role in protecting Plasmodium as the pathogen pursues infection of its host. The findings were published April 25th in the open-access journal PLoS Pathogens.*

Worldwide, the annual death toll of malaria exceeds 1 million, and children under the age of five are its major victims. The Plasmodium parasite that causes malaria in humans is transmitted through the bites of infected mosquitoes. Once inside the human body, the parasite initially develops in the liver and subsequently, upon release, infects red blood cells. After infecting host red blood cells, a rapid growth ensues, supported by the parasite’s consumption of hemoglobin, the oxygen-transporting protein that constitutes a massive 90% of the total protein present inside each red blood cell. Destruction on this scale releases large quantities of heme, the prosthetic group responsible for oxygen transport in hemoglobin. Free heme is extremely damaging and to protect itself from this toxic onslaught, the parasite utilizes a novel mechanism where it rapidly converts heme into a crystalline material known as hemozoin.

Dr. Dharmendar Rathore, Assistant Professor at VBI, remarked: “We discovered HDP as part of a functional genomics initiative that is focused on the identification of malaria proteins involved in disease pathology. A combination of cellular and biochemical approaches allowed us to rigorously characterize HDP. It appears that HDP has a number of striking features that make it a promising candidate as a drug target. HDP is not only capable of rapidly converting heme into its non-toxic counterpart hemozoin, but it is highly conserved in all the species of the parasite and also appears to be critical for its survival.” He added: “The beauty of this discovery is that, while HDP has robust interactions with heme, it lacks homology to any of the known heme-binding proteins and has therefore eluded detection during previous attempts by several groups to identify parasite factors responsible for hemozoin formation.”