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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
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Evolution of high-level resistance during low-level antibiotic exposure
Erik Wistrand-Yuen1, Michael Knopp1, Karin Hjort1
1Department of Medical Biochemistry and Microbiology, Uppsala University, 75237, Uppsala, Sweden.
Nature Communications
|April 25, 2018
Summary
Low antibiotic levels can drive the evolution of antibiotic resistance in bacteria. Salmonella enterica evolved high-level streptomycin resistance through multiple small mutations, not just lethal selection pathways.
Area of Science:
- Microbiology
- Evolutionary Biology
- Genetics
Background:
- Sub-inhibitory concentrations (sub-MIC) of antibiotics are prevalent in the environment.
- The evolutionary mechanisms driving antibiotic resistance under low-level antibiotic exposure are not well understood.
Purpose of the Study:
- To investigate the evolutionary pathways of high-level antibiotic resistance development in Salmonella enterica exposed to sub-MIC streptomycin.
- To compare resistance mechanisms under sub-lethal versus lethal antibiotic selection pressures.
Main Methods:
- Exposure of Salmonella enterica to sub-MIC levels of streptomycin.
- Genomic analysis to identify mutations conferring resistance.
- Comparison of resistance mechanisms with those observed under lethal selection.
Main Results:
- Salmonella enterica evolved high-level streptomycin resistance through novel mechanisms distinct from lethal selection.
- Sub-MIC selection resulted in the accumulation of multiple small-effect mutations.
- Identified three key mechanisms: ribosomal RNA target alteration (gidB), reduced aminoglycoside uptake (cyoB, nuoG, trkH), and AadA enzyme induction (znuA).
Conclusions:
- The strength of antibiotic selective pressure significantly influences evolutionary trajectories.
- Even weak selective pressures, such as sub-MIC antibiotic levels, can lead to the evolution of high-level antibiotic resistance.
- Understanding these pathways is crucial for predicting and combating antibiotic resistance spread.
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