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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
Phages limit the evolution of bacterial antibiotic resistance in experimental microcosms
Quan-Guo Zhang1, Angus Buckling
1State Key Laboratory of Earth Surface Processes and Resource Ecology and MOE Key Laboratory for Biodiversity Science and Ecological Engineering, Beijing Normal University Beijing, China.
Abstract:
The evolution of multi-antibiotic resistance in bacterial pathogens, often resulting from de novo mutations, is creating a public health crisis. Phages show promise for combating antibiotic-resistant bacteria, the efficacy of which, however, may also be limited by resistance evolution. Here, we suggest that phages may be used as supplements to antibiotics in treating initially sensitive bacteria to prevent resistance evolution, as phages are unaffected by most antibiotics and there should be little cross-resistance to antibiotics and phages. In vitro experiments using the bacterium Pseudomonas fluorescens, a lytic phage, and the antibiotic kanamycin supported this prediction: an antibiotic-phage combination dramatically decreased the chance of bacterial population survival that indicates resistance evolution, compared with antibiotic treatment alone, whereas the phage alone did not affect bacterial survival. This effect of the combined treatment in preventing resistance evolution was robust to immigration of bacteria from an untreated environment, but not to immigration from environment where the bacteria had coevolved with the phage. By contrast, an isogenic hypermutable strain constructed from the wild-type P. fluorescens evolved resistance to all treatments regardless of immigration, but typically suffered very large fitness costs. These results suggest that an antibiotic-phage combination may show promise as an antimicrobial strategy.
Insights
Combining phages and antibiotics can prevent bacterial resistance evolution. This dual approach significantly reduces bacterial survival and resistance compared to antibiotics alone, offering a promising antimicrobial strategy.
Area of Science:
- Microbiology
- Evolutionary Biology
- Public Health
Background:
- Multi-antibiotic resistance in bacteria is a growing public health crisis.
- Bacteriophages (phages) show potential against antibiotic-resistant bacteria, but phage resistance can also emerge.
- Combining antibiotics and phages may prevent resistance evolution in bacteria.
Purpose of the Study:
- To investigate if combining antibiotics and phages can prevent the evolution of bacterial resistance.
- To assess the efficacy of antibiotic-phage combinations compared to monotherapies.
Main Methods:
- In vitro experiments using Pseudomonas fluorescens, a lytic phage, and the antibiotic kanamycin.
- Testing the impact of antibiotic-phage combinations, antibiotic-only, and phage-only treatments on bacterial survival and resistance evolution.
- Evaluating the robustness of the combined treatment against bacterial immigration from different environments.
Main Results:
- An antibiotic-phage combination significantly decreased bacterial population survival indicative of resistance evolution compared to antibiotic treatment alone.
- Phage-only treatment did not affect bacterial survival.
- The combined treatment's resistance-preventing effect was robust to immigration from untreated environments but not from phage-coevolved environments.
- A hypermutable bacterial strain evolved resistance to all treatments but incurred significant fitness costs.
Conclusions:
- Antibiotic-phage combinations show promise in preventing bacterial resistance evolution.
- This strategy may be effective for treating initially sensitive bacterial infections.
- Further research is warranted to explore the clinical applicability of combined antimicrobial approaches.
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