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Putting bacterial antibiotic resistance into reverse
Date:4/25/2010

p 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."

To develop such a screen, Kishony and his group first had to figure how this unusual interaction works.

"Fast growing bacteria like E. coli are optimized to balance their protein and DNA activity to grow and divide as quickly as the surrounding environment allows," Kishony explains. "However, when we exposed E. coli to the ciprofloxacin, we found that their optimization disappeared."

"We expected that since the bacteria would have more difficulty copying DNA, they would slow down their protein synthesis, too," Kishony continues. "But they didn't; they kept churning out proteins, which only added to their stress." However, once they added the tetracycline and protein synthesis was also reduced in the E. coli, they actually grew better than before. They then confirmed the idea that production of ribosomes - the cell components that make proteins - is too high under DNA stress by engineering E. coli strains that have fewer ribosomes than regular bacteria. While these mutants grew a more slowly in normal conditions, they grew faster under ciprofloxacin inhibition of DNA synthesis.

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.


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Contact: Nicole Kresge
nkresge@asbmb.org
202-316-5447
Federation of American Societies for Experimental Biology
Source:Eurekalert

Page: 1 2

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