Study sheds light on how malaria parasite hijacks human red blood cells

Washington, July 9 : A new study from the Walter and Eliza Hall Institute of Medical Research in Australia is shedding light on how malaria parasite hijacks human red blood cells and fuels disease progression.

The study led by Alan Cowman showed how parasite survives in and totally changes red blood cells.

They have uncovered proteins produced by the malaria parasite that allows it to hijack and remodel human red blood cells, leaving the oxygen-carrying cells stiff and sticky. Those effects on the blood cells play a major role in the development of malaria.

Cowman believes "there may be some way of inhibiting these processes by drugs or possibly a live vaccine."

Once the Plasmodium falciparum, responsible for malaria enters the blood it multiplies inside red blood cells (also known as erythrocytes), which is responsible for severity and mortality associated with the disease.

After the parasite invades, the red cells undergo profound structural and morphological changes, dramatically altering their physical properties and impairing circulation.

In contrast to normal red blood cells, parasitized cells are rigid and adhere to the lining of the blood vessels and other cell types.

These changes are apparently caused by proteins produced by parasite inside the cells of its host and exports across several membranes out to the red cell itself.

In the present study, the researchers were particularly interested in finding proteins required for "trafficking" PfEMP1 (a protein which allows infected cells to stick to blood vessels) to the infected erythrocyte surface.

In search of those players, the researchers developed mutant strains of P. falciparum each lacking one of 83 genes known or predicted to play a role in the red cell remodeling process.

Their screen turned up eight genes encoding proteins required for export of the PfEMP1 and assembly of knobs. Additionally, they show that multiple proteins play a role in generating increased rigidity of infected erythrocytes.

The researchers wrote, "We have used a gene knockout approach on a scale not previously attempted in this organism to address the role of P. falciparum proteins that are exported into the parasite-infected erythrocyte.

"Collectively these proteins act like the secretion systems seen in bacteria in which pathogenicity arises from secreted proteins that interact with host cells by direct injection or by their presence in the extracellular milieu. ...It may be valuable to adopt approaches being tested in bacteria in which these systems are the target of new therapeutic approaches aimed at minimizing pathogen virulence," they added.

The study appears in July 11th issue of the journal Cell, a Cell Press publication.

ANI