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Free radicals may cause mutations that create superbugs

February 12, 2010

Debra Black

STAFF REPORTER

New research has found that low levels of antibiotics boost the production of free radicals which in turn cause mutations in the DNA of bacteria, causing superbugs that are resistant to treatment, according to a study published in a recent issue of Molecular Cell.

The study, conducted at Boston University by Jim Collins and a team of researchers, examined the impact of low doses or nonlethal doses of antibiotics and their production of free radicals on bacteria. And the results may one day change the way bacterial infections that are immune to some drugs are treated.

In earlier experiments Collins’ lab found that the antibiotics that kill bacteria actually stimulate the production of free radicals and these free radicals actually contribute to the lethal effect of antibiotics on bacteria. But that’s in the case of lethal doses of antibiotics.

But the team wondered what happens when the level of antibiotics is not as high as is needed or are at the low levels found in water or the food chain. Then there’s a totally different effect. The free radicals actually cause mutation in the gene structure of the bacteria and make them resistant to drug therapy.

“If you don’t kill them off you have a zoo of mutants being produced,” said Collins, a professor of biomedical engineering at both Boston University and Harvard University Friday in an interview with the Star.

For Collins the research indicates that the problem of drug resistant bacteria or super bugs “is even worse” than researchers thought. And it also means that “we need to be careful and make sure we don’t have low levels of antibiotics in our food sources, our water,” he said. “And we make sure people complete their full course of antibiotics and don’t demand antibiotics for a cold.”

The most recent study done by Collins, along with Michael Kohanski and Mark DePristo, shows the more problematic side of free radicals has significant implications for increasing super-resistance in bacteria. Free radicals can be bad because they can cause damage to DNA, lipids and proteins in the body, Collins said.

It appears, according to Collins’ lab’s most recent work, that when sub lethal (or low doses) of antibiotics are used on bacteria the free radicals produced substantially damage the DNA of the bacteria and cause mutations.

That would be a moot point if the bacteria were killed off, Collins said. But because the dose of antibiotics isn’t enough to kill the germs superbugs or drug-resistant bacteria are created.

The most recent study “showed us the free radicals being produced as a result of drug treatment are in fact also contributing to the mutations that are occurring,” said Kowalski, a PhD student working with Collins in an interview. The discovery provides additional insight into how these microbes could be adapting and evolving, he said.

But more importantly, it could also one day provide some alternative ways to treat superbugs and additional targets for designing new drugs to not only kill the bacteria but also limit the mutations.

Superdrug resistant bacteria have become an increasingly difficult problem in North America in recent years, especially with the increased use of antibiotics in the food chain as well as the overuse of antibiotics. Bacteria such as C-difficile and MRSA are causing problems and in some cases deaths in Canadian hospitals because they are super resistant to some antibiotics.

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