Herbicide curbs human parasite's spread.

Herbicide curbs human parasite's spread

In the search for new drugs against human parasitic diseases, a popular weed killer has emerged as a promising candidate.

Farmers in the United States and abroad use an herbicide called trifluralin to eliminate grasses and some broadleaf weeds in fields of soybean, cotton, safflower and other crops. But new research on human and mouse cells shows that the herbicide also stops the parasite Leishmania mexicana dead in its tracks while leaving the mammalian cells unharmed. This suggests that some close chemical cousin of trifluralin may eventually prove therapeutic for many of the world's 10 to 20 million people infected with leishmania protozoans. These single-celled organisms, common in many developing countries, cause skin ulcers and potentially fatal organ damage.

The odd discovery had its beginnings in work performed two years ago. Dunne Fong and his colleagues at Rutgers University in Piscataway. N.J., determined the exact sequence of amino acids that form a leishmania protein called beta-tubulin, a key component of tiny fibers called microtubules. Microtobules provide cells with structural support and are critical to cell division.

Although leishmania parasites belong in the animal kingdom, Fong's team found that the amino acid sequence of leishmania beta-tubulin has more in common with plant tubulin sequences than with animal ones. Reasoning that chemicals toxic to plant tubulin might, if specific enough, interfere with leishmania cells without bothering human tubulin, Fong and Marion Man-Ying Chan began searching for such a compound.

The Rutgers reseachers tested serveral herbicides whose modus operandi is to interfere with plant beta-tubulin. They report inthe Aug. 24 SCIENCE that trifluralin binds to L. mexicana beta-tubulin but not to mammalian beta-tubulin. Even at extremely low concentrations, the herbicide interferes with the parasite's replication, cutting interfectious spread by half in cultured human and mouse cells, they say. Yet at 20 times this dose, it still leaves the mammalian cells unscathed.

Fong and Chan don't propose spraying the herbicide on onfected people. For one thing, they note, the compound breaks down very quickly in sunlight--an advantage for an agricultural chemical not meant to build up in the environment, but a draw back for a drug applied to skin. Instead, they suggest that scientists might design a closely related compound with anti-leishmania activity and superior pharmacological traits. Moreover, they say, "there may be other potentially useful . . . agents [against these and other paratsites] among the commercially available herbicides."

Health officials estimate that parasitic diseases such as leishmaniasis, malaria, amoebiasis and toxoplasmosis affect more than one-quarter of the world's population, or well in excess of 1 billion people. For many of these diseases--including leishmaniasis, transmitted by a bitting sandfly -- current drug treatments remain unsatisfactory at best.