Smart Bugs Keep Outsmarting The Scientists

In the arms race between man and bacteria, the outcome is still in doubt. By 1947, six years after the discovery of penicillin, doctors had noticed the first hint of trouble: They needed ever higher doses to kill bacteria. Since then, even with an arsenal of antibiotics, bacteria have become increasingly resistant to all but a couple of the strongest drugs.

Unfortunately, resistance to antibiotics spreads. First detected in Australia in 1967, highly resistant pneumonia bacteria appeared in South Africa in 1977, causing many deaths. Since then, the bugs have shown up in Spain, in parts of the U. S.--including New York--and in Eastern Europe. In Hungary in 1975, 18% of the pneumonia bacteria found in patients were resistant to most common antibiotics. By 1989, that was over 50%--and 70% in children. "Multiresistance is the biggest threat to drugs," says Alexander Tomasz, head of the microbiology lab at New York's Rockefeller University.

TRADING PLACES. In nursing homes and big city hospitals, there are reports that 50% or more of the staphylococcus bacteria--the type that causes infections in deep wounds and around implants such as artificial hips and heart valves--are resistant to penicillin derivatives that make up 60% of all antibiotics. Dr. Victor L. Yu, professor of medicine at the University of Pittsburgh, blames the overuse of antibiotics for this. Now, the hunt is on to find out how bacteria can be so smart--and to devise ways to beat their defenses.

Antibiotics work by blocking the action of a key protein the bacteria need to survive. But bacteria can trade genetic material with each other, circumventing a drug. To fend off penicillin, for instance, staphylococcus bacteria imported genes that let them make an enzyme that degrades the antibiotic. In response, researchers strengthened the antibiotic's chemical bonds. So the bacteria imported genes that let them make a decoy protein to tie up the antibiotic. Resistant pneumonia bacteria use a more complicated method.

How bad could it get? "We don't expect a disaster like the black plague," says Tomasz. "But we used to have quite an arsenal of antibiotics. Now we have only a few" that are completely effective. One that is typically used when others fail is vancomycin, a "back burner" drug developed years ago by Eli Lilly & Co. and only recently revived. But last year, researchers found a relatively harmless species of bacteria that contained a vancomycin-resistant gene. The fear is that this gene could find its way into staphylococcus. Another drug, Merck & Co.'s imipenem-cilastatin, is considered the "nuclear bomb of the field," says Tomasz. It is used only when nothing else works. But, he adds, some bacteria have been reported as being resistant to it.

Tomasz is hoping that discoveries of how microbes evade drugs will lead to new classes of compounds that control bacteria. It's a race researchers have to win. Because if they can't stay one step ahead of nature's simplest creatures, then humans could once again suffer the epidemics that used to spread misery around the world.

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