E. Coli Learns Resistance from Low Doses of Antibiotics

The acquisition of resistance to amoxicillin, tetracycline, and enrofloxacin by Escherichia coli MG 1655 was examined by exposing growing cells to constant or stepwise increasing concentrations of these compounds. The minimal inhibitory concentration (MIC) of E. coli for amoxicillin increased from 4–8 to 32 μg/ml after growth in the presence of 1.25 or 2.5 μg/ml. By stepwise increasing the exposure, an MIC of 512 μg/ml was reached. This high MIC was maintained after removal of the antibiotics, whereas the lesser increase after exposure to low levels was reversed, indicating that the high MIC was due to a genetic change, but the lower one to phenotypic adaptation only. The MIC for tetracycline increased from 2 μg/ml to maximally 32 μg/ml. The MIC decreased to control levels in the absence of tetracycline, so no genetic changes seem to have occurred. The MIC for enrofloxacin increased from 0.25 μg/ml to maximally 512 μg/ml depending on the concentration during growth. These data mostly support the “radical-based” theory that bactericidal antibiotics induce a common mechanism that contributes to cell killing. Our findings indicate that exposure to low levels of antibiotics causes an increase in MIC above the concentration that the cells were exposed to. The implication is that exposure to low levels of antibiotics should be prevented as much as possible, because this causes resistance far more than high concentrations that inhibit growth or kill the cell and thus prevent acquisition of resistance

From press release:

E. coli bacteria exposed to three common antibiotics were more likely to develop antibiotic resistance following low-level antibiotic exposure than after exposure to high concentrations that would kill the bacteria or inhibit their growth, according to a timely article in Microbial Drug Resistance, a peer-reviewed journal published by Mary Ann Liebert, Inc.

E. coli bacteria in food and water supplies have been responsible for disease outbreaks and deaths around the world in recent years. The current outbreak in Europe has sickened thousands of individuals and caused multiple deaths and life-threatening complications in hundreds of persons infected with a new strain of E. coli.

Bacterial resistance to commonly prescribed antibiotics is an enormous and growing problem, largely due to misuse of antibiotics to treat non-bacterial infections and environmental exposure of the bacteria to low levels of antibiotics used, for example, in agriculture.

In the article "De Novo Acquisition of Resistance to Three Antibiotics by Escherichia coli," the authors studied the mechanisms by which E. coli acquire resistance to three common antibiotics: amoxicillin, tetracycline, and enrofloxacin. Depending on the antibiotic and the level of exposure, different mechanisms may come into play. The authors report that exposure to antibiotics at relatively low levels--below those needed to inhibit growth of the bacteria--are more likely to result in the development of antibiotic resistance. "Exposure to low levels of antibiotics therefore clearly poses most risk," a finding that "contradicts one of the main assumptions made questioning the threat of usage of antibiotics in food animals," conclude the authors.