Worms and Wonder Drugs

Saturday, March 01, 1997
Many diseases once easily treatable with antibiotics-- tuberculosis, for example--have turned into killers again. Why? Bacteria have evolved. They not only shrug off penicillin and other treatments, but they actually thrive in, and in some cases even require, the presence of antibiotics. Many researchers are concerned that the development of new antibiotics may not keep pace with the appearance of resistant bacterial strains. In the wake of such alarming developments, John Webster’s research comes as welcome news. Webster, a parasitologist at Simon Fraser University in British Columbia, has discovered a new class of chemical compounds that could serve as powerful antibiotics and perhaps even anticancer agents.

The new compounds come from Xenorhabdus, bacteria that live inside certain species of soil-dwelling microscopic worms called nematodes, which Webster has been studying for some 20 years. These bacteria cannot survive in the soil and can reproduce only inside insects. They are thus content to reside harmlessly inside the nematode until the worm encounters their breeding ground.

When that happens, the nematode burrows into the hapless insect and releases a packet of bacteria. The bacteria start feeding on the insect and reproduce furiously. The nematode starts feeding on the multiplying bacteria, and then the nematode starts reproducing, so everybody’s happy except the insect, which eventually dies and bursts open, says Webster.

What intrigued Webster was that the bacteria, during their feeding frenzy, produce chemicals that kill competing bacteria. Webster and his colleagues began studying the chemicals while investigating the antibiotic effect of dumping millions of nematodes into soil to control insect crop pests.

He and his colleagues have isolated several novel compounds from Xenorhabdus. One, which Webster calls nematophin, is a powerful antifungal and antibacterial agent. Another, dubbed xenorxide, attacks human lung, breast, prostate, and colon cancer cells, while leaving healthy cells alone, at least in a petri dish. One major advantage of these new chemicals, says Webster, is that even low doses are highly effective against bacteria now immune to the penicillin family of antibiotics. We believe our substances have an advantage, and the resistance buildup will be slower, says Webster. The bacteria will have to start at ground zero instead of halfway up the ladder.

In lab tests the chemicals don’t appear to be toxic in mice or rats. Since little is known about why these compounds work so well, however, Webster says it will be at least six to eight years before the drugs have any human application. But we’re very hopeful, he adds.
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