New Antibiotics Put Bacteria in a Bind

By Greene, Lindsey A. | Environmental Health Perspectives, December 2000 | Go to article overview

New Antibiotics Put Bacteria in a Bind


Greene, Lindsey A., Environmental Health Perspectives


For decades, antibiotics have enjoyed "miracle drug" status, but because overuse and improper use are leading to increased bacterial resistance, many of these wonder drugs no longer work. However, recent studies at The Scripps Research Institute in La Jolla, California, may offer new hope for effective antibiotics.

Antibiotics work by destroying either the proteins that build a bacterium's cell wall or the protein-producing ribosomes. But resistant bacteria have altered their cell walls or ribosomes to withstand the drugs' action. So Chi-Huey Wong, a chemist at The Scripps Research Institute, decided to foil bacteria in a new way, by stepping in to the process earlier and preventing the creation of proteins in the first place.

In the 31 May 2000 issue of the Journal of the American Chemical Society, Wong and colleagues describe how they achieved this by targeting bacterial RNA, which builds proteins using information from the DNA. By binding aminoglycoside antibiotics to bacterial RNA, Wong is disrupting the synthesis of proteins at the point where resistance usually begins, and at the same time suppressing the creation of the bacterial enzymes that cause antibiotic resistance.

"We were interested in targeting the RNA, so we chose to study aminoglycosides since they are known to bind to RNA," says Wong. The aminoglycoside family, first discovered in the mid-1940s, includes streptomycin and neomycin. These antibiotics are usually injected or applied topically. The aminoglycosides are highly toxic, and particularly affect the ears and kidneys, although the damage they cause is usually minor and reversible.

Wong and colleagues chose to work with neamine, the simplest of the aminoglycoside antibiotics, structurally speaking. The group created several different dimers of neamine and tested them for their antibiotic activity and their ability to bind to RNA and disrupt protein synthesis. They identified several dimers of neamine that had high binding ability and were highly effective at killing bacteria such as Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. …

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