Key points:
- A new study challenges the traditional view that antibiotic resistance emerges from pathogens that acquire new mutations.
- Samples from ICU patients suggest that instead, highly diverse pathogen communities harbor pre-existing resistant genotypes.
- The results suggest that interventions aimed at limiting the spread of bacteria between patients may provide a powerful approach to combat rising antibiotic resistance.
Traditionally, resistance to antibiotic treatment evolves because of natural selection for new genetic mutations that occur during an individual’s infection. However, a new study from researchers at the University of Oxford is challenging this view—and providing an alternative.
Published in Nature Communications, the new study suggests patients are commonly co-infected by multiple pathogen clones—rather than a single genetic strain—with resistance emerging as a result of selection for pre-existing resistant clones, rather than new mutations.
For the study, the researchers obtained samples from, 35 ICU patients in 12 European hospitals, looking for the common, antibiotic-resistant Pseudomonas aeruginosa.
Most patients in the study (approximately two-thirds) were infected by a single Pseudomonas strain. Resistance evolved in some of these patients due to the spread of new resistance mutations that occurred during infection, supporting the conventional model. However, the authors found that the remaining one-third of patients were actually infected by multiple strains of Pseudomonas.
Additionally, resistance increased by about 20% more when patients with mixed strain infections were treated with antibiotics, compared with patients with single strain infections. The rapid increase in resistance in patients with mixed strain infections was driven by natural selection for pre-existing resistant strains that were already present at the onset of antibiotic treatment. According to the researchers, these strains usually made up a minority of the pathogen population that was present at the start of antibiotic treatment, but the antibiotic resistance genes that they carried gave them a strong selective advantage under antibiotic treatment.
Although resistance emerged more quickly in multi-strain infections, the team says the study findings suggest it may also be lost more rapidly in these conditions. When samples from single strain and mixed strain patients were cultured in the absence of antibiotics, the resistance strains grew more slowly compared with the other strains. This supports the hypothesis that resistance genes carry fitness trade-offs.
The scientists conclude that interventions aimed at limiting the spread of bacteria between patients (such as improved sanitation and infection control measures) may be a more effective intervention to combat antibiotic resistance than interventions that aim to prevent new resistance mutations arising during infection, such as drugs that decrease the bacterial mutation rate.