Low-levels of antibiotics can produce high-levels of resistance

The findings are significant because they show that high-level antibiotic resistance doesn’t only occur when bacteria are exposed to high levels of antibiotics; it can also evolve in response to low-level antibiotic exposure, driven by mutations in genes and that have not previously been associated with antibiotic resistance. This suggests that the number of genes associated with antibiotic resistance could be underestimated, and that these genes could act as a “stepping stone” for the evolution of clinically significant resistance.
Low levels of antibiotics in animals, environment
The suggestion that even small amounts of antibiotic exposure could be contributing to antibiotic resistance has big implications. Livestock and poultry producers routinely give their animals sub-therapeutic doses of antibiotics to prevent disease, a practice many experts believe contributes to antibiotic resistance.
In addition, a growing body of research conducted in recent years has documented the presence of antibiotics and antibiotic residues in rivers, lakes, tidal estuaries, and wastewater around the world, with households, hospitals, pharmaceutical factories, and farms as the likely sources.
According to a recent report from the United Nations Environment Program, up to 80 percent of antibiotics used by humans are excreted un-metabolized through urine and feces into sewage systems and flow into wastewater treatment plants that also treat water from hospitals and industrial facilities. Because these plants aren’t designed to fully remove antibiotics and other pharmaceuticals from wastewater, they end up being released into surface waters. Likewise, antibiotics used in food-animal production get excreted in manure and show up in farm soils or get carried into nearby lakes and streams with other untreated agricultural runoff.
Although the extent of environmental contamination from human and animal antibiotic use, and role that this contamination plays in the development of clinically relevant antibiotic resistance, are not yet clear, many experts believe the presence of even trace amounts of antibiotics in the environment is not without consequences.
Lead study author Dan Andersson, a professor in the department of medical biochemistry and microbiology at Uppsala, said the study provides evidence that the very low concentrations of antibiotics present in a number of environments could contribute to antibiotic resistance evolution. But how significant a contributor, in comparison to the selection pressure caused by antibiotic use in patients, is hard to say.
“It’s likely to contribute, but it’s hard to put a number on it,” Andersson said in an email.
Andersson and his colleagues are planning similar studies with other antibiotics and other bacterial species, and hope to test their findings outside of the lab. “We want to examine if this selection process occurs outside of the laboratory, in natural settings,” he said.
— Read more in Erik Wistrand-Yuen et al., “Evolution of high-level resistance during low-level antibiotic exposure,” Nature Communications 9, Article number: 1599 (23 April 2018) (doi:10.1038/s41467-018-04059-1)