[off-topic] Resistance Is Futile

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Resistance Is Futile

By F. Service

ScienceNOW Daily News

28 March 2007

CHICAGO, ILLINOIS--Antibiotics have saved countless lives since

Fleming discovered penicillin in 1927. But in recent years, microbes have

responded by developing resistance to many of the most powerful antibiotics,

threatening to undermine one of modern medicine's greatest achievements. This

evolution of antimicrobial resistance may one day become a thing of the past.

California-based researchers reported here today at the semiannual meeting of

the American Chemical Society that they've discovered compounds that inhibit the

ability of bacteria to produce mutations in their genetic code. The compounds

are not antibiotics in themselves. But they could lead to future medicines that

could be given alongside powerful antibiotics to prevent bugs from quickly

outwitting the drugs.

The new compounds evolved out of the discovery more than 30 years ago that

deleting certain genes in bacteria prevents the microbes from evolving

resistance when exposed to antibiotics. Biologists later found that when

microbes are not under such antibiotic pressure, they copy their DNA using

enzymes known as DNA polymerases that make very few mistakes. But when the

pressure is on, the bugs turn to normally dormant DNA polymerases that are far

more error prone. These errors create genetic mutations in their progeny, some

of which prove beneficial, and thereby encourage the selection of new traits

such as antibiotic resistance.

Prompted by those results, 2 years ago Floyd Romesberg, a chemist at the Scripps

Research Institute in San Diego, California, and colleagues reported that both

in vitro and animal studies showed that a gene called LexA serves as one of the

key " on " switches for the error-prone DNA polymerase. For their current work,

the Scripps researchers looked for small, druglike molecules that inhibit LexA

and thereby stymie mutations in bugs exposed to ciprofloxacin, an antibiotic

that itself prevents DNA replication. After screening more than 100,000

compounds, the researchers found several potent LexA inhibitors that all but

halt the ability of bacteria to mutate and also easily get inside microbial

cells, a notoriously difficult challenge for would-be drugs.

Full story

http://sciencenow.sciencemag.org:80/cgi/content/full/2007/328/3?etoc