Small groups with big impact: antibiotic heteroresistance more common than thought

When selecting antibiotics for treatment of bacterial infections, physicians often rely on regular drug sensitivity tests conducted on bacterial samples from the patients. Still, treatments are sometimes unsuccessful. A new study led by Dan Andersson from Uppsala University provides evidence that heteroresistance, the presence of a resistant subpopulation in a main population of susceptible cells, is part of the explanation.

Using the SciLifeLab National Genomics Infrastructure (NGI), the researchers investigated the existence of heteroresistance in bacteria isolated from patients, as well as the underlying mechanisms behind the phenomenon. Four different bacterial species causing infectious diseases in humans were analyzed, and 28 types of antibiotics were utilized. Surprisingly, their results demonstrated that more than a fourth of the bacteria-antibiotic-combinations studied contained resistant subpopulations.

The researchers also show that heteroresistance is a result of spontaneous gene amplifications of resistance genes, causing antibiotic-sensitive bacteria with only one resistance gene copy to grow resistant when additional copies arise. As they are very instable, these gene amplifications are fickle, and a resistant bacterium can quickly become sensitive to antibiotics again. This trait makes heteroresistance difficult to detect and study, posing challenges to hospital laboratories the world over.

Read the full paper in Nature Microbiology
Read a press release by Uppsala University (or: in Swedish)