Scientists seek to reverse bacterial antibiotic resistance

WASHINGTON - The use of antibiotics to treat bacterial infections spurs emergence of resistant strains, forcing the use of additional drugs leading to further multi-drug resistance, according to scientists.

Researchers are using this discovery to identify novel drug combinations that could hinder the development of resistance but still act effectively.

Harvard researcher Roy Kishony says: “Normally, when clinicians administer a multi-drug regimen, they do so because the drugs act synergistically and speed up bacterial killing.”

However, Kishony’s lab has focused on the opposite phenomenon: antibiotic interactions that have a suppressive effect, namely when the combined inhibitory effect of using the two drugs together is weaker than that of one of the drugs alone.

Kishony and his team identified the suppressive interaction in E. coli, discovering that a combination of tetracycline - which prevents bacteria from making proteins - and ciprofloxacin - which prevents them from copying their DNA - was not as good as slowing down bacterial growth as one of the antibiotics (ciprofloxacin) by itself.

Kishony notes that this suppressive interaction can halt bacterial evolution, because any bacteria that develops a resistance to tetracycline will lose its suppressive effect against ciprofloxacin and die off.

While such a weakened antibiotic combination is not great from a clinical standpoint, the Kishony lab is using this discovery to set up a drug screening system that could identify novel drug combinations that could hinder the development of resistance but still act highly effectively.

“Typical drug searches look for absolute killing effects and choose the strongest candidates,” he says. “Our approach is going to ask how these drugs affect the competition between resistant versus sensitive bacterial strains.”

Kishony notes that their preliminary work on the development of a screen for drugs that put resistance in a disadvantage looks promising, and hopes that it would lead to the identification of novel drugs that select against resistance, said a Harvard release.

These findings were presented at the American Society for Biochemistry and Molecular Biology’s annual meeting evolution of antibiotic resistance.