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Weed killers kill malaria too
By Kate Dalke

New herbicides and antibiotics could be the next anti-malarial drugs. Some of the same compounds that kill weeds and bacteria also kill the malaria parasite.

Both herbicides and antibacterials disable an ancient organelle in the parasite that resembles a chloroplast found in plants. The drugs are generally safe for people because they target specific proteins in the parasite without harming the host.

Green organelles called apicoplasts (left); round balls in center are malaria parasites (middle); and green apicoplasts inside parasites (right).

"Antibacterials and herbicides are two really promising categories of potential anti-malarial drugs," says Geoffrey McFadden of the University of Melbourne in Australia.

In a new study, McFadden and his colleagues have discovered over 400 newly identified parasite proteins, which could be disabled by new herbicides and antibiotics. Many of these proteins are found in plants and bacteria too.

The word herbicide evokes some noxious images, but McFadden says that it is a case of the worst and most notorious ones getting all the attention. He points out that many herbicides are safe and non-toxic.

Indeed, one drug has already proven safe and effective in humans and is in clinical trials in the West African nation of Gabon.

The drug, called fosmidomycin, was originally developed as an antibiotic for urinary infections in the 1980s, and has also been used in herbicides. Researchers rediscovered the drug's use for malaria two years ago when they found it disables a specific enzyme in the malaria parasite.

"Fosmidomycin looks very promising," says Peter G. Kremsner of the University of Tübingen, Germany, who leads the drug trial. It kills even those malaria parasites already resistant to other drugs. The parasite's resistance to current drugs is a growing problem.

Malaria parasite inside human blood cells, with green plastid, several blue nuclei and red food vacuole.

Fosmidomycin cured 80 percent of patients in a small trial last year. But some patients had recurring parasites in their bloodstream so the researchers may combine several drugs in treatments.

The malaria parasite's genome has speeded the search for new drug targets. German researchers found the fosmidomycin target by searching unfinished parasite DNA sequences in a computer database from the Plasmodium falciparum genome project. The genome was later sequenced in October 2002.

"The genome has shown us all of these new targets," says Alan F. Cowman of the Walter and Eliza Hall Institute of Medical Research in Melbourne, who collaborated with McFadden.

"All of a sudden, we have 400 drug targets where previously there were none," Cowman says. Over the next few years there will be a slew of antibacterials and herbicides that come through and work better than the original drugs."

See related GNN article
»The Parasite and the Mosquito: Malaria's deadly partners are sequenced

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Foth, B.J. et al. Dissecting apicoplast targeting in the malaria parasite Plasmodium falciparum. Science 299, 705-708 (January 31, 2003).
Missinou, M. et al. Fosmidomycin for malaria. The Lancet 360, 1941-1942 (December 14, 2002).
Jomaa, H. et al. Inhibitors of the nonmevalonate pathway of isopreoid biosynthesis as antimalarial drugs. Science 285, 1573-1576 (September 3, 1999).

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