NEW TARGET FOUND FOR DRUG TREATMENTS
AIMED AT SINGLE-CELLED PARASITES

BLOOMINGTON, Ind. -- Researchers at Indiana University and the University of Pennsylvania have discovered what they hope will be a new target in the battle against some single-celled parasites, including the malaria-causing Plasmodium and Toxoplasma, which often cause AIDS-related infections.

In the March 7 issue of the journal Science, molecular evolutionist Jeff Palmer and botanist Charles Delwiche of Indiana University, along with parasitologists Sabine Kohler and David Roos of the University of Pennsylvania and their colleagues, report that chloroplast-like plastids recently found in a group of single-celled parasites apparently originated in algal cells that were engulfed as the parasite was evolving.

The functions of the plastids in the parasites are unknown (they no longer perform photosynthesis), but the fact that they remained after being engulfed suggests they play an important role in this particular class of parasites. And because the cells of humans and other mammalian hosts of the parasites don't have such plastids, the plastids are likely targets for drug therapies.

It is commonly understood that eukaryotic cells (those of animals, plants, fungi, and protists) acquired some of their most important components, such as the photosynthesizing chloroplast, when they engulfed simpler bacterial cells. The study conducted by Palmer, Roos and six co-authors supports the idea that a more complex cell, in this case an algal cell, can be taken up by, and become an integral part of, another cell. In addition to the implications for new drug treatments, the findings also suggest that the process of cells engulfing other cells may have been more common in molecular evolution than previously suspected.

The researchers first suspected they were looking at a case of microbiological thievery when they discovered DNA in the parasites that closely resembled DNA within the chloroplasts of green algae. They next determined that the purloined DNA's new home was within a separate organelle that appears to be surrounded by four membranes. The number of membranes would support the idea that the DNA came from an algal cell's chloroplast. The chloroplast has two membranes of its own, in addition to the algal cell's outer membrane. When engulfed, these three membranes would be retained, in addition to a remnant of the parasite cell's own engulfing membrane, for a total of four.

While the number of membranes alone is not conclusive evidence of the researchers' theory, genetic analysis conducted by Palmer's lab lends further support. They found that the genes of the chloroplast-like plastids more closely resemble the genes of plastids of green algae than comparable genes in photosynthetic bacteria where chloroplasts originated.

Understanding the origin and genetic structure of these novel plastids in parasitic cells is the first step in understanding how to eradicate them. Biomedical researchers must now determine the critical functions of the plastids to make it possible to design drugs that inhibit these functions and shut down the parasite without harming the host.

For more information, contact Jeff Austin, 812-855-0084 or 812-855-3911, jeaustin@indiana.edu