Common additive thwarts malaria parasite
An antimicrobial chemical used in mouthwashes has emerged in the unlikely role of malaria fighter. Experiments in mice show that this substance, triclosan, wipes out the parasite responsible for rodent malaria. In test-tube studies, the compound also kills the parasite responsible for most severe cases of malaria in people, scientists in India report.
The researchers found that triclosan binds to an enzyme called FabI in Plasmodium falciparum, the parasite infecting people. Without a supply of functional FabI, P. falciparum can’t make some fatty acids that are essential for its survival, says study coauthor Namita Surolia, a biochemist at the Jawaharlal Nehru Centre for Advanced Scientific Research in Bangalore.
The study, described in the February Nature Medicine, is also the first to identify the gene that encodes FabI in the parasite. Surolia collaborated with Avadesha Surolia of the Indian Institute of Science, also in Bangalore.
After finding that triclosan inhibits P. falciparum in a test tube, the researchers infected 10 mice with Plasmodium berghei, the rodent malaria parasite. They then gave four of the mice daily injections of triclosan over 4 days but withheld the chemical from the other six mice. After 8 days, the treated mice had undetectable blood concentrations of P. berghei, whereas the six untreated mice had died from the infection.
The researchers report that the treated mice were still free of parasites 6 weeks later. “If the drug was unstable, the parasite population would be expected to re-emerge, but it hadn’t,” says Matthew Berriman, a biologist at the Sanger Centre of the Wellcome Trust Genome Campus in Cambridge, England.
In the United States, manufacturers put triclosan in toothpaste, soaps, deodorants, skin creams, and acne medications–topical applications intended to kill microbes. Scientists have limited knowledge of the chemical’s effects, including possible toxicity, when taken internally, says Lars Hviid, a parasitologist at the Center for Medical Parasitology in Copenhagen.
Testing for those effects, even of a substance approved for other uses, can be expensive, he notes. Nevertheless, fatty acid biosynthesis in the parasite is “an attractive target” for scientists, Hviid says. Fatty acid production requires FabI in P. falciparum but not in mammals. Therefore, drugs specifically aimed at this enzyme shouldn’t disrupt normal cell functions in people, Berriman says.
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P. falciparum has become resistant to several drugs, making the need for new treatments critical. Some resistance to triclosan itself has emerged in bacteria. Thus, the chemical might work best as part of a combination assault on malaria, Hviid says.
Although triclosan neutralizes only one enzyme in the parasite’s fatty acid production, “other enzymes involved may also be susceptible to inhibition,” Hviid says.
Scientists also need to seek new targets outside fatty acid biosynthesis, says Namita Surolia. She plans to test triclosan next on monkeys infected with yet another Plasmodium.