Now DeRisi and Yeh have shown that the sole essential function of the apicoplast while the parasite is in the blood is to produce a single chemical known as isopentenyl pyrophosphate (IPP), a necessary building block the parasite uses to construct a variety of other molecules.
They discovered this by growing samples of Plasmodium falciparum within red blood cells in the test tube. If they treated the parasite with antibiotic drugs that kill the apicoplast, the parasites would all die. If they fed the parasites IPP at the same time, they lived even though the parasites lost the organelle completely over time.
The work provides a new tool for probing the basic biology of the Plasmodium parasite, and it also suggests a new way of discovering promising new drugs to fight malaria. While many previous drug-screening efforts have identified multitudes of compounds that appear to inhibit growth of the parasites, most are without a known target within the parasites. Knowing the target of a drug greatly enables the necessary process of medicinal chemistry, in which the compound is optimized with respect to the target. Now, DeRisi and Yeh's discovery has provided a simple tool to determine whether any particular drug candidate targets the apicoplast.
The attenuated form of the parasite also provides an intriguing hypothetical vaccine candidate and one that would be relatively cheap to produce, DeRisi said. However, he cautioned, the history of malaria control is filled with failed efforts, and several past vaccines have fallen short. Only time and clinical trials will tell if this is a viable solution to the problem.
"This parasite has clearly evolved
|Contact: Jason Socrates Bardi|
University of California - San Francisco