WASHINGTON D.C.—In the war against malaria, researchers have recruited an unlikely ally: a seaweed found in Fiji. The seaweed, a red alga, produces an antifungal compound, which tests show kills the malarial parasite. If the compound proves effective in animal and human studies, it could become the newest weapon against a disease that kills more than a million people a year.
The malarial parasite has proved a formidable enemy. It has evolved the ability to evade every drug developed to kill it, often within just a few years. Already, resistance has appeared in Cambodia against the latest compound in the anti-malaria arsenal: artemisinin.
But Julia Kubanek wasn't really thinking about malaria when she first saw the algae. A chemical ecologist at Georgia Institute of Technology in Atlanta, she and her colleagues want to know how marine plants and animals defend themselves against infections. As anyone who has gotten an infection from swimming in the ocean with a cut knows all too well, seawater is full of dangerous bacteria. In Fiji, she and her colleagues collect fistfuls of seaweeds and other marine species to look for natural antibiotics. As part of those tests, they screen compounds isolated from those organisms not just for antibiotic potential but also for anti-cancer, anti-HIV, and other biomedical properties.
In 2005, Kubanek's group discovered that the red alga, Callophycus serratus, had a family of unusual ring-shaped compounds called bromophycolides that were particularly effective against certain fungi. In 2009, the biomedical screening revealed that one had strong antimalarial properties.
Kubanek has now determined the probable mechanism underlying its ability to kill the malaria parasite. By linking a fluorescing molecular tag to the bromophycolide, she and her colleagues were able to track the compound in red blood cells. Malarial parasites infect red blood cells and they thrive on hemoglobin, the body's oxygen-carrying molecules. As the parasites break hemoglobin down, they release heme, a pigment that is toxic to them. To protect themselves, the parasites crystallize the heme and store it in a separate chamber. But the bromophycolide prevents this crystallization. Thus the heme accumulates, poisoning the parasite, Kubanek reported here today at the annual meeting of the American Association for the Advancement of Science (which publishes ScienceNOW). "It seems to be preventing the transformation from a compound that is toxic to one that's not toxic," she said.
Chloroquine, an antimalarial drug with widespread resistance, works in a similar way. However, this seaweed compound still killed chloroquine-resistant parasites, she reported. Next, she and her colleagues will see if this compound still kills the parasite in mice. In the meantime, others are working to modify it to make it more effective and simpler to mass produce. At least one group is trying to make the compound from scratch in the lab.
"There are still a lot of details to be worked out," says Ian Baldwin, a chemical ecologist at the Max Planck Institute for Chemical Ecology in Jena,
Germany. "But if the drug keeps heme still active, that may be the death of the [parasite]."