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Low level antibiotics mutate bacteria and create superbugs

Kathleen Blanchard's picture

Boston University researchers have shown for the first time how taking low levels of antibiotics that don't quite destroy bacteria can turn them into superbugs, making bacteria drug resistant. When drugs fail to completely destroy bacteria they become even stronger - one of the reasons your doctor always tells you to finish your antibiotics.

Boston University Professor James J. Collins who led the study explains, "In effect, what doesn't kill them makes them stronger. These findings drive home the need for tighter regulations on the use of antibiotics, especially in agriculture; for doctors to be more disciplined in their prescription of antibiotics; and for patients to be more disciplined in following their prescriptions." Antibiotics that kill bacteria cause a reaction that makes them shed DNA - but low level antibiotics mutate their DNA, making bacteria stronger and resistant to a wide array of drugs.

Collins and his team demonstrated two years ago how high doses of antibiotics lead to the death of bacteria through DNA damage. Antibiotics treatment produces free radical inside bacterial cells that ultimately kills germs. In the new study, the scientists found that low levels of antibiotics actually end up turning bacteria into superbugs that can resist multiple antibiotics. Free radicals produced by antibiotic drugs merely mutate DNA providing protection to the bacteria from a variety of drugs.

"We know free radicals damage DNA, and when that happens, DNA repair systems get called into play that are known to introduce mistakes, or mutations," said Collins. "We arrived at the hypothesis that sub-lethal levels of antibiotics could bump up the mutation rate via the production of free radicals, and lead to the dramatic emergence of multi-drug resistance."

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The researchers tested the effect of low level antibiotics on strains of E. coli and Staphylococcus. The scientists observed the effect of five different antibiotics on the bacteria, finding that doses that were less than lethal to the germs made them resistant to other antibiotics. The team was able to find the gene sequence that caused mutations creating the superbugs. In some cases, the bacteria remained susceptible to the original antibiotic but developed resistance to others.

Low level antibiotics actually helped the bacteria mutate. Collins says, "Because you're not killing with the antibiotics, you're allowing many different types of mutants to survive. We discovered that in this zoo of mutants, you can actually have a mutant that could be killed by the antibiotic that produced the mutation but, as a result of its mutation, be resistant to other antibiotics."

The findings have implications for public health. Farmers often use low level antibiotics in livestock feed that can create superbugs. Physicians who prescribe antibiotics for viral infections may also be contributing to the problem of antibiotic resistance, and individuals who fail to complete their course of antibiotic prescriptions could be helping bacteria mutate, contributing to the creation of superbugs that are resistant to antibiotics.

Now that researchers better understand the effect of low level antibiotics and how bacteria mutate and become multidrug resistant, new antibiotics could emerge that stop bacteria from repairing their DNA and turning into superbugs. Findings ways to stop antibiotic resistance might also be accomplished by developing antibiotics that boost free radical production to destroy bacterial cells using low doses of antibiotics.

Molecular Cell