The work is reported in Current Biology by Joshua Zimmerberg and colleagues at the U.S. National Institutes of Health. 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 behaviour 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 centre. 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 neighbouring red blood cells.
Further experiments involving labelled 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.
MEDICA.de; Source: Cell Press