By specially tagging the outer and inner membranes of red blood cellsinfected with the malaria parasite and tracking the cellular changesthat precede the cell bursting event that disperses parasites to otherblood cells, a group of researchers has deepened our understanding ofhow the malaria pathogen destroys the cells in which it resides. Thework is reported in Current Biology by Joshua Zimmerberg and colleaguesat the U.S. National Institutes of Health.
Malaria devastates humanity: Approximately every 10 seconds, anotherchild dies as a result of a malarial infection. Globally, it is thethird biggest killer, and it mostly kills children. The emergence ofall-drug-resistant strains of Plasmodium falciparum, the parasiteresponsible for most human malarial disease, is a frightening newreality that mandates aggressive research to develop new vaccines anddrugs, particularly to uncover new targets for therapeutic agents. Amajor area of current ignorance is the mechanism by which parasites arereleased from the infected red blood cells within which they multiply.
To learn more about this release process, in their new work theresearchers used high-quality microscopy and a "Nan crystal"fluorescent tag that allowed them to follow the behavior of membranesof infected cells during an extended period of time. The authorsdiscovered that many minutes before release, infected cells lookirregular, resembling a fried egg, with the parasites bunched togetherin the center. They found that just prior to release, cells round upand 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 ofrelease itself, cellular membranes fold upon themselves and bubble intosmall vesicles, allowing the newly born parasites (in this stage theyare called merozoites) to infect neighboring red blood cells. Furtherexperiments involving labeled membrane components showed that there isno membrane fusion during release, but that instead it is likely that abuild-up of pressure occurs inside the cell, causing cell-membranerupture and subsequent merozoite release. This idea was substantiatedby experiments showing that shrinking cells to prevent their burstingstopped the release stage and thus stopped the infection from furtherdevelopment.
The researchers include Svetlana Glushakova, Dan Yin, Tao Li, andJoshua Zimmerberg of the National Institutes of Health in Bethesda,Maryland. This research was supported by the Intramural ResearchProgram of the NIH, NICHD, and NASA/NIH Center for Three-DimensionalTissue Cultures.
Glushakova et al.: "Membrane transformation during malariaparasite release from human red blood cells." Publishing in CurrentBiology, Vol. 15, pages 1645-1650, September 20, 2005. DOI10.1016/j.cub.2005.07.067 www.current-biology.com
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