Do Low-Level Antibiotics Create Mutant “Zoos”?

A new generation of drug-resistant bacteria could be coming faster, and through a different mechanism, than researchers had expected.

That is the scary finding of a new study by William Fairfield Warren Distinguished Professor James J. Collins, a College of Engineering professor of biomedical engineering and codirector of the Center for BioDynamics, and five coauthors, published in the February 12 edition of Molecular Cell.

Collins and his team found that after giving nonlethal doses of specific antibiotics to strains of E. coli and staphylococcus bacteria, both culprits in a range of dangerous infections, the bacteria’s DNA mutated in ways that protected it from a wider range of antibiotics. Collins, a 2003 MacArthur “Genius” Award winner and a Howard Hughes Medical Institute investigator, believes the lower doses of antibiotics speed up bacteria’s mutation rates.

In that case, what was intended as a cure could have the opposite effect, spawning a bacterial “zoo” that resists treatment.

Inevitable sci-fi scenarios of mutant plagues aside, what are the implications of these findings?

BU Today: Did the study’s results surprise you?
Collins: Some aspects were surprising, but the majority were concerning. Most surprising was that sublethal levels of antibiotic can lead to the development of mutants that can still be killed by the primary antibiotic. But the real problem is that these low levels of antibiotic serve as active mutagens by triggering free radicals, which leads to a surprising situation in which you have a zoo of mutants.

What kind of response are you getting from the clinical world, and from drug companies?
So far we’ve gotten a very positive response from the clinical community and the media. I don’t expect to hear from drug companies, which no longer do research and development on antibiotics. They view the antibiotic market as not financially attractive compared to markets associated with chronic conditions or lifestyle drugs like Viagra.

Is there any medical reason for prescribing antibiotics in doses too low to kill bacteria?
Doctors would not prescribe low levels per se. The problem could arise when a patient stops taking a presciption after a few days instead of completing the full course. Also, even with clinical levels of antibiotics, portions of the body see lower levels, because the antibiotic is unevenly distributed, and this can increase risk.

Who is most at risk from drug-resistant bacteria?
Kids, individuals who have compromised immune systems, and the elderly. Remember that MRSA (methicillin-resistant staphylococcus aureus), the drug-resistant strain of staph, arose in hospitals as a result of overuse of antibiotics, and now it’s escaped into the community.

Should we be concerned about meat from livestock treated with antibiotics?
Farmers use these lower, sublethal levels of antibiotics as a preventive, and that is concerning, because the antibiotics ramp up the mutation rate. I’m not an expert on the agriculture industry, but I have heard that farmers are seeing a rise in resistant strains. If animal meat and products contain antibiotics, they can be transferred to our bodies when we eat them, and this would trigger these effects.

What are the most common misconceptions about antibiotics?
The biggest misunderstanding is if you have an infection, you should take antibiotics. But they target only bacterial infections, so if you have a cold or a viral flu, antibiotics aren’t going to help you. And doctors prescribe them like candy, often to appease patients who come in with colds. So a doctor might say, here, take it for a number of days and you’ll be fine.

I think it would be better if doctors gave these patients sugar pills. There are also people who have unused prescription antibiotics lying around the house. When they feel a sore throat coming on they take a pill, thinking that it works as a preventive. This could create more problems and doesn’t solve any.

Based on this study, what would you advise health providers?
We should minimize antibiotics, in the agriculture sphere as well as in the clinic. We should use them only for patients who really need them, and those patients should take the full course. Third, we should develop new antibiotics that are unlikely to mutate. This can be done by targeting the error-prone DNA repair systems.

Will you be working on that?
We’re exploring additional ways antibiotic resistance can arise. We’ll have a few interesting stories. There is definitely more to come.

Susan Seligson can be reached at sueselig@bu.edu.