New research from Uppsala University shows that even low concentrations of antibiotics can lead to the development of high antibiotic resistance in bacteria.


Antibiotics resistant antibiotics are a global and growing problem in health care. In order to avoid further resistance development, it is important to understand where and how antibiotic resistance in bacteria occurs.

In the current study, published in Nature Communications, the researchers have investigated how exposure of low levels of antibiotics for a long time contributes to the development of antibiotic resistance in bacteria. During an antibiotic treatment, a large proportion of the antibiotic dose will be excreted through the urine in unchanged and active form, and through the sewage can then spread to watercourses, lakes and fields. As a consequence, these environments may contain low levels of antibiotics. In some parts of the world, large amounts of antibiotics are used in meat production and fish farms, where small doses of antibiotics are added to the animal feed to make the animals grow faster. This causes bacteria in their intestines to be exposed to low levels of antibiotics for a long time, and these bacteria can then infect people via, for example, food.

In the article, researchers show that even low concentrations of antibiotics play a major part in the development of resistance. The study showed that bacteria exposed to low doses of antibiotics over time developed resistance to antibiotic levels that were more than a thousand times higher than the initial level to which they were exposed. It was also found that mutations in the bacteria DNA that cause resistance are of a different type than if they were exposed to high doses. During the course of the experiment, the bacteria eventually accumulated several mutations, each of which gave a low resistance, but together gave a very high resistance. In addition, mutations occurred mainly in genes previously not considered as typical resistance genes, suggesting that the number of genes that can contribute to resistance development is heavily underestimated.

"The results are interesting because they show that even the very low antibiotic concentrations found in many environments can lead to high levels of resistance and contribute to the problem of resistance," said Professor Dan I Andersson, Head of Study.

The research has been funded by the Swedish Research Council

Evolution of high-level resistance during low-level antibiotic exposure, Nature Communications, DOI: 10.1038/s41467-018-04059-1.

Linda Koffmar