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Disrupting common parasites' ability to 'talk' to each other reduces infection
Date:1/9/2008

or approximately a decade that protozoan parasites like T. gondii and those that cause malaria contain many plant-like pathways, or groups of genes or proteins put to use for a particular biological task. The common ancestor of these parasites incorporated an algal cell millions of years ago. This endosymbiotic relationship results in the incorporated organism becoming a regular part of the larger organism's cell structure. The parasites can make use of the algae's genes, many of which were transferred to the parasite's nucleus to control processes in a structure that is a remnant of the original algal cells.

That earlier revelation led to ongoing efforts to develop drugs that block plant-like proteins parasites use to synthesize metabolically important structures or compounds. However, until this study, no one had found the parasites using a plant-like protein for signaling purposes.

"Signals are sometimes even better targets for drug development than biosynthetic pathways," says Sibley. "Taking out a biosynthetic pathway means you take away one thing from the parasite. But if you can successfully disable a key signal, this may potentially disrupt many more aspects of the parasite's metabolism."

Kisaburo Nagamune, Ph.D., formerly a postdoctoral fellow in Sibley's laboratory, found the ABA pathway in T. gondii while searching the parasite's genome for pathways linked to calcium signalling. Researchers knew that calcium signaling was important to the parasite's ability to control its complex reproductive cycle, but a search for genes similar to the calcium signaling pathways found in mammalian cells, such as the calcium receptors or channels that are common in heart cells and neurons, found few analogs in T. gondii.

ABA has many prominent roles in plant biology, including regulation of flowering and seed dormancy. A series of experiments led by Nagamune, now an assistant professor at Tsukuba University in Japan, showed that ABA hel
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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

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