Soil search suggests broad roots for antibiotic resistance

NEW HAVEN, Conn. — Despite Star Trek baddies’ claims about its futility, resistance, at least to antibiotics, is everywhere.

Bacteria developing resistance to antibiotic drugs have become a major medical problem worldwide. Despite years of studying the genes that allow bacteria to fight off antibiotics, scientists still aren’t sure where the genes come from in the first place, says Jo Handelsman, a microbiologist at Yale University.

Some people blame soil as the source of antibiotic-resistance genes, and there are logical reasons to think it might be. Soil is home to tons of microbes, including many fungi that naturally produce antibiotic compounds, so it makes sense that bacteria living in the soil would have genes that could counter that particular type of chemical warfare.

But Handelsman’s research is showing that that kind of circumstantial evidence won’t hold up under scrutiny. She has a fondness for soil — do not call it dirt, please — and thinks it and its microbial residents have been unfairly maligned. She spoke November 7 at the Council for the Advancement of Science Writing meeting.

She and her colleagues took soil from three different places: undisturbed islands in the wilds of Alaska that don’t have any medical or agricultural exposures to antibiotics; an apple orchard that is regularly sprayed with the antibiotic streptomycin to combat a bacterial infection of trees; and an agricultural station in Madison, Wis.

Because less than 1 percent of bacteria in soil can be grown in the lab, the researchers had to use different methods to figure out whether soil bacteria have antibiotic-resistance genes. Instead of trying to grow individual types of bacteria in the lab, the researchers isolated DNA from the entire soil sample, what Handelsman calls a metagenomic approach. Then the scientists put chunks of the DNA into common E. coli bacteria to test if any of those chunks contained genes for antibiotic resistance.

Handelsman and her colleagues did find antibiotic-resistance genes in the soil samples, but those genes were distinct from those that make bacteria resistant to antibiotics in medical settings. For instance, two types of genes that allow bacteria to survive treatment with the antibiotic kanamycin are found in people. But the kanamycin-resistance genes found in soil bacteria are of a different variety. The team found that the resistant genes from the soil bacteria from the orchard and the Alaskan islands tended to fuse together two different antibiotic-defeating mechanisms. Those types of compound genes are not usually found in bacteria that can be grown in the lab, Handelsman says.

Soil bacteria have genes that can fight off pretty much any type of antibiotic, including a man-made drug that does not occur in nature. The researchers found genes for resistance to a synthetic antibiotic called fluorphenicol in Alaskan soil samples. Those genes encode a molecular pump that helps keep the drug out of the bacterial cells. Handelsman says that the bacteria probably use the pump to get rid of other things, but are also able to use it for pumping out antibiotics.

The team also examined samples taken from both the soil and from the intestines of people who work in the apple orchard. Researchers were particularly interested in looking for genes for streptomycin resistance in these samples because the antibiotic is regularly sprayed at the orchard, which could theoretically encourage the growth of resistant strains. Doctors are especially worried about resistance to that antibiotic because it is often used to treat tuberculosis infections. Yet the team found few streptomycin-resistance genes from the soil directly under sprayed trees, Handelsman says. The resistance genes the researchers found in the workers and the soil were different from each other and also different from the genes that help bacteria fend off streptomycin in the clinic.

So while antibiotic-resistance genes are everywhere in the soil, they aren’t the ones causing medical problems for people. No one knows exactly where the antibiotic resistance genes seen in people actually originated, but it’s clear that soil bacteria aren’t the scapegoats some had thought.

“The simple-minded predictions have almost always been wrong,” Handelsman said.