Malaria is a disease caused by parasites that are transmitted to humans through the bite of infected mosquitoes. Globally, this disease causes more than one million deaths each year, most prevalent in Africa and Asia. The parasite infects red blood cells (hemoglobin-containing cells that carry oxygen throughout the body) and hijacks the support structure within the cell.
Some people are known to be naturally resistant to the serious effects of malaria and scientists have wondered for decades how the function of their resistance to malaria could occur. Now, a new research reveals the mystery.
It has been known for decades that some people in Africa and elsewhere, who have a gene mutation that causes sickle-cell anemia, also have resistance to malaria. This is because their red blood cells contain unusual S forms hemoglobin, which results in aggregation of hemoglobin in the cells. Having only one mutated copy of the S hemoglobin makes one a carrier of symptoms. While those who has two copies, produces symptoms of sickle-cell anemia. Both cases of mutations provide some protection against malaria. Another mutation, hemoglobin C, causes hemolytic anemia when two copies of the mutation is present and is also a form of protection against malaria.
In a paper published in the scientific journal Science, researcher Marek Cyrklaff of Heidelberg University, Germany, and colleagues reported that an unusual form of hemoglobin in red blood cells prevents the malaria parasite, Plasmodium falciparum, from hijacking of actin filaments that provide a scaffolding framework in the cell. They compared healthy red blood cells containing hemoglobin and infected with ‘normal’ with healthy and infected cells that contain hemoglobin S or hemoglobin C.
By using cryoelekton tomography, the researchers found that in normal cells, actin protein filaments cells were short and located below the outer cell membrane, where they provide structural support for cells to make it strong, but flexible enough to pass through the smallest blood vessels.
In cells infected with normal hemoglobin, they found the protein actin are on the long filaments, which the parasites is used to build intracellular (cytoskeleton) bridges, in the cell for transporting the proteins produced (adhesin), to the cell surface. The effect of the adhesin is to make the cells stick together side by side and to plug the cells into the blood vessel wall which causes an inflammatory characteristic of malaria response.
In the cells of hemoglobin S and C, the bridge can not be complete and adhesin can not be effectively transported to the cell surface, thereby reducing the stiffness of the cell. The scientists also found that the hemoglobin C and S is more easily oxidized than the shape that is not mutated.
Malaria is most often treated with quinine, but clinical trials of vaccines are now being conducted in Africa by GlaxoSmithKline and the results look promising with 65 percent effectiveness rate. Recent research suggests that malaria drugs could be developed by disrupting the ability of the parasite by using actin filaments.Tagged with: malaria, malaria resistance,