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Antibiotics Versus Bacteria

Antibiotic drugs are lethal to bacteria. And they can be lifesaving for people suffering from serious bacterial infections such as pneumonia and meningitis. But some bacteria are fighting back by developing resistance to antibiotics. And a few of these determined bugs manage to not only resist death by antibiotics, but also turn the lethal drugs into food.

Drug resistance is a serious and worsening problem that threatens to set medical care back to a time when antibiotics were not yet discovered and infectious disease was the No. 1 cause of death worldwide.

Modern industrial and agricultural practices are hastening the rise of antibiotic resistance by saturating the environment with active drugs. In India and China, which together produce the vast majority of the world’s antibiotics, pharmaceutical factories sometimes dump antibiotic-laden waste into local waterways. In the United States, some farmers add antibiotics to their animal feed to help their livestock grow, which produces waste loaded with the drugs.

Bacteria easily share genetic material. So when antibiotics infiltrate the water and soil, resident bacteria respond by spreading antibiotic-resistance genes through the community.

Until recently, scientists have understood little about how bacteria manage to safely eat antibiotics. But new research from a team of scientists at Washington University School of Medicine has illuminated key steps in the process. As it turns out, environmental antibiotic contamination promotes drug resistance and undermines our ability to treat bacterial infections. And researchers say this information could lead to new ways to eliminate antibiotics from our land and water.

“Ten years ago, we stumbled onto the fact that bacteria can eat antibiotics, and everyone was shocked by it,” says Gautum Dantas, PhD, a scientist working in the fields of pathology, immunology, molecular microbiology and biomedical engineering. “But now it’s beginning to make sense. It’s just carbon, and wherever there’s carbon, somebody will figure out how to eat it. Now that we understand how these bacteria do it, we can start thinking of ways to use this ability to get rid of antibiotics where they are causing harm.”

Dantas, senior author of the study, Terence Crofts, PhD, first author, and their colleagues wanted to understand how some environmental bacteria not  only withstand antibiotics, but feed on them. They studied four distantly related species of soil bacteria that all flourish on a diet of penicillin alone. Penicillin was the first antibiotic discovered, but it has fallen out of favor because of resistance. Other members of the penicillin family, including amoxicillin and ampicillin, are still effective and widely prescribed to treat bacterial infections.

The research team found three distinct sets of genes that became active while the bacteria ate penicillin but inactive while the bacteria ate sugar. The three sets of genes correspond to three steps bacteria take to transform a lethal compound into a meal. All of the bacteria start by neutralizing the dangerous part of the antibiotic. Once the toxin is disarmed, they snip off a tasty portion and eat it.

Understanding the steps involved in converting an antibiotic into food could help researchers bioengineer bacteria to clean up soil and waterways contaminated with drugs and thereby slow the spread of drug resistance. The soil bacteria that naturally eat antibiotics are finicky and difficult to work with. But a more tractable species such as E. coli potentially could be engineered to feed on antibiotics in polluted land  or water.

Crofts and Dantas showed they could give E. coli the ability to survive and thrive on penicillin. The bacterium normally requires sugar, but with some genetic modification and the addition of a key protein, it flourished on a sugar-free diet of penicillin.

"With some smart engineering, we may be able to modify bacteria to break down antibiotics in the environment,” Crofts says.

Any such bioengineering project would have to include a plan to speed up the antibiotic-eating process. The way soil bacteria naturally remove antibiotics from the environment is effective but slow. They couldn’t possibly handle the amounts of antibiotics near pharmaceutical factories and in sewage facilities.

“You couldn’t just douse a field with these soil bacteria today and expect them to clean everything up,” Dantas says. “But now we know how they do it. It is much easier to improve on something that you already have than to try to design a system from scratch.”

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