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Low levels of antibiotics cause multidrug resistance in 'superbugs'
Date:2/11/2010

BOSTON (Feb. 11, 2010) For years, doctors have warned patients to finish their antibiotic prescriptions or risk a renewed infection by a "superbug" that can mount a more powerful defense against the same drug. But a new study by Boston University biomedical engineers indicates that treating bacteria with levels of antibiotics insufficient to kill them produces germs that are cross-resistant to a wide range of antibiotics.

In the Feb. 12 issue of Molecular Cell, research led by Boston University Professor James J. Collins details for the first time the biomolecular process that produces superbugs. When administered in lethal levels, antibiotics trigger a fatal chain reaction within the bacteria that shreds the cell's DNA. But, when the level of antibiotic is less than lethal the same reaction causes DNA mutations that are not only survivable, but actually protect the bacteria from numerous antibiotics beyond the one it was exposed to.

"In effect, what doesn't kill them makes them stronger," said Collins, who is also a Howard Hughes Medical Institute investigator. "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."

Two years ago, Collins together with graduate student Michael Kohanski and post-doctoral fellow Mark DePristo -- proved that when applied in lethal doses, antibiotics stimulate the production of reactive oxygen species (ROS) molecules, or free radicals that damage DNA, protein and lipids in bacterial cells, contributing to their demise. In the new study, the same co-authors demonstrated that the free radicals produced by a sub-lethal dose of an antibiotic accelerate mutations that protect against a variety of antibiotics other than the administered drug.

"We know free radicals damage DNA, and when t
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Contact: Michael Seele
mseele@bu.edu
617-353-9766
Boston University College of Engineering
Source:Eurekalert

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