Out of concern over the growing number of antibiotic resistant bacteria, federal policymakers will phase out the practice of giving food animals low-doses of antibiotics to promote growth. In an effort to discover whether science backs up the potential policy change, Associate Professor in Veterinary and Biomedical Sciences at the College of Veterinary Medicine (CVM) Tim Johnson, Ph.D., studied the issue.
For the past decade, Johnson has been using bacterial genomics to discover how antibiotic resistance spreads from one bacterial cell to another. One culprit, he says, is the plasmid. Plasmids are small DNA molecules found inside bacterial cells.
“Plasmids are mobile and can spread between cells within a bacterial species, or even between cells of unrelated bacterial species,” says Johnson. “Plasmids that carry genes encoding drug resistance can spread them from cell to cell, strain to strain, and species to species.”
A single plasmid can carry—and spread—resistance for up to 10 antibiotics, notes Johnson. In fact, he adds, each time plasmids spread resistance they spread the entire package. A plasmid that is resistant to three antibiotics, for example, will spread all three resistances, and one resistant to 10 antibiotics will spread all 10.
The practice of giving food animals regular low doses of antibiotics has been standard for about five decades, but since antibiotic resistance is growing, the U.S. Food and Drug Administration is now phasing out the practice in animal agriculture. “The assumption is that lower doses given on a regular basis are worse than higher doses that are given to treat active infections,” says Johnson.
To find out whether that premise is true, Johnson and other CVM veterinary researchers, Richard Isaacson, Randall Singer, and Peter Davies, conducted a controlled animal study on 20 pigs split into four groups. The control group of pigs was given feed without antibiotics. The second group was given the same feed and was inoculated with a non-pathogenic E. coli bacteria carrying a plasmid encoding drug resistance. The third group was inoculated with the same non-pathogenic E. coli and treated daily with a low dose of tetracycline in feed at 50 grams per ton, which is standard industry practice. The fourth and final group was inoculated with the non-pathogenic E. coli and treated twice for seven days with a high dose of tetracycline in feed at 350 grams per ton, with low-dose concentrations given between the high-dose treatments.
Johnson then cultured fecal samples from the pigs over a five-week period to track the selection of the inoculated strain and the movement of the resistance-carrying plasmid to other bacteria in the pigs’ gastrointestinal systems.
“We went into the experiment expecting both the low-dose and the high-dose antibiotic treatments to increase resistance,” says Johnson. “To our surprise that didn’t happen. It only happened with the high-dose treatment group.” The high dose of tetracycline caused the resistance-carrying plasmid to move into other strains and species of bacteria, increasing the overall number of resistant bacteria.
“The low-dose treatment had zero effect on resistance-carrying plasmids,” Johnson notes. As low-dose antibiotic use is eliminated from animal agriculture, Johnson says that bacterial infections could increase requiring even more use of high-dose antibiotic treatments, which in turn could hasten the spread of antibiotic resistance.
“Some people think that if we get rid of the low dose use of antibiotics, the superbugs are going to disappear,” he says. “But we don’t have the science to support that.”
Beginning in 2016, a prescription from a veterinarian will be needed to treat bacterial infections in food animals, which will help eliminate indiscriminate on-farm use of high-dose antibiotic treatments.
Johnson’s study, “In Vivo Transmission of an IncA/C Plasmid in Escherichia coli Depends on Tetracycline Concentration, and Acquisition of the Plasmid Results in a Variable Cost of Fitness,” was published in the May 2015 issue of Applied and Environmental Microbiology.
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