Identifying new stages in release of malaria parasite provides leads in search for drugs

21 Jun 2010

Paul Chinnock

Source: Current Biology (see original article or PDF)

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Citation: Glushakova S, Humphrey G, Leikina E, Balaban A, Miller J, Zimmerberg J. New Stages in the Program of Malaria Parasite Egress Imaged in Normal and Sickle Erythrocytes. Curr Biol. 2010 May 26. [Epub ahead of print]

Little has been known as to how malaria parasites escape from an infected red blood cell to spread around the rest of their human host. US researchers have reported that they have identified two steps in the process. By interfering with one of these stages it may be possible to develop new malaria drugs.

To conduct the study, the researchers examined red blood cells from volunteers with sickle cell anaemia, an inherited disease in which these cells have a curved, or sickle shaped, appearance. The misshapen cells can clog blood vessels and hinder blood flow. The mutation that causes sickle cell anaemia is prevalent in parts of the world where malaria is common. Although having two copies of the mutated gene causes sickle cell anaemia, having only one copy confers a resistance to malaria.

In normal red blood cells, the rupture of cells and subsequent release of the parasites proceeds almost instantaneously, and is very difficult to observe. However, the researchers found that in sickle cells this process occurs at a much slower rate, enabling them to observe it. By following the progression of the disease in sickle cells infected with the malaria parasite Plasmodium falciparum, the researchers were able to document stages in the process that had not been observed before.

Typically, a malaria parasite reproduces inside a sac within a red blood cell. In two days, the parasite multiplies, filling the sac until the new parasites burst out of their host cell. It had been widely believed the pressure of the growing parasites simply caused the sac to burst, but the researchers uncovered a more complex process. Several minutes before rupturing, the parasite-filled sac inside the cell swells and the remainder of the cell shrinks. Moreover, seconds before the infected cell bursts, the cell membrane turns porous, like a leaky plastic bag.

The researchers went on to show that a sealing agent, poloxamine, could stop cells from rupturing and releasing the parasites. They now plan to study the effects of poloxamine and similar compounds on the bursting process in hopes of developing a new malaria treatment.

Note: This study has been published in a journal that is not open access. To read it in full, a subscription to Current Biology is therefore required. Readers working in institutions in some developing countries may be able to access it through the HINARI programme.

2010 Elsevier Ltd