How the malaria pathogen destroys the cells in which it resides, deeper understanding

Main Category: Tropical Diseases
Article Date: 23 Sep 2005 - 0:00 PDT

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By specially tagging the outer and inner membranes of red blood cells infected with the malaria parasite and tracking the cellular changes that precede the cell bursting event that disperses parasites to other blood cells, a group of researchers has deepened our understanding of how the malaria pathogen destroys the cells in which it resides. The work is reported in Current Biology by Joshua Zimmerberg and colleagues at the U.S. National Institutes of Health.

Malaria devastates humanity: Approximately every 10 seconds, another child dies as a result of a malarial infection. Globally, it is the third biggest killer, and it mostly kills children. The emergence of all-drug-resistant strains of Plasmodium falciparum, the parasite responsible for most human malarial disease, is a frightening new reality that mandates aggressive research to develop new vaccines and drugs, particularly to uncover new targets for therapeutic agents. A major area of current ignorance is the mechanism by which parasites are released from the infected red blood cells within which they multiply.

To learn more about this release process, in their new work the researchers used high-quality microscopy and a "Nan crystal" fluorescent tag that allowed them to follow the behavior of membranes of infected cells during an extended period of time. The authors discovered that many minutes before release, infected cells look irregular, resembling a fried egg, with the parasites bunched together in the center. They found that just prior to release, cells round up and become very symmetric, resembling a flower, with the parasites (present beneath the cell-membrane surface) appearing like the petals.

The researchers showed that at the seemingly explosive event of release itself, cellular membranes fold upon themselves and bubble into small vesicles, allowing the newly born parasites (in this stage they are called merozoites) to infect neighboring red blood cells. Further experiments involving labeled membrane components showed that there is no membrane fusion during release, but that instead it is likely that a build-up of pressure occurs inside the cell, causing cell-membrane rupture and subsequent merozoite release.

This idea was substantiated by experiments showing that shrinking cells to prevent their bursting stopped the release stage and thus stopped the infection from further development.

The researchers include Svetlana Glushakova, Dan Yin, Tao Li, and Joshua Zimmerberg of the National Institutes of Health in Bethesda, Maryland. This research was supported by the Intramural Research Program of the NIH, NICHD, and NASA/NIH Center for Three-Dimensional Tissue Cultures.

Glushakova et al.: "Membrane transformation during malaria parasite release from human red blood cells." Publishing in Current Biology, Vol. 15, pages 1645-1650, September 20, 2005. DOI 10.1016/j.cub.2005.07.067 http://www.current-biology.com

Heidi Hardman
hhardman@cell.com
1-617-397-2879
Cell Press
http://www.cellpress.com

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