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New penicillin booby-traps bacteria.

For years after its introduction as a drug in the 1940s, penicillin served as the first-line defense against bacterial infections. Bacteria evolved, however, into new strains with the ability to survive the drug. Now, many infections are resistant to penicillin and other antibiotics, fueling fears that doctors may soon run out of tools to keep these diseases in check.

A new study suggests that, with modification, penicillin might still have some punch left. Researchers at the University of Limerick in Ireland have attached a molecular booby trap to penicillin that can potentially defeat resistant bacteria. Timothy P. Smyth and his colleagues reported their strategy on Oct. 9 in the online version of the Journal of Organic Chemistry.

Bacterial strains resistant to penicillin have enzymes called beta-lactamases, which clip a crucial ring of the penicillin molecule, rendering it ineffective. "Over 190 of these enzymes have been identified so far, and the count is rising," Smyth says.

He and his colleagues chemically modified penicillin so that it releases a molecular fragment when a beta-lactamase cuts the ring. The fragment can be designed to kill bacteria. The most effective penicillin molecule they have synthesized to date kills Escherichia coli in the test tube, but only at high doses. Any bacteria that do not produce a beta-lactamase would be destroyed by the regular action of the antibiotic.

A strategy currently used to overcome resistant bacteria combines penicillin with compounds that block beta-lactamases, thus protecting the antibiotic. Bacteria, however, quickly develop beta-lactamases that don't bind those substances. To avoid that problem, the Limerick team uses the enzyme itself as a trigger to release and activate the lethal fragment, Smyth says.

Although the scheme looks promising, he adds, "there is some way to go yet to deliver a therapeutically useful drug."
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Author:Wu, Corinna
Publication:Science News
Article Type:Brief Article
Date:Oct 24, 1998
Words:295
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