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Updated: Jul 4, 2026

Quantification of Plasmid-Mediated Antibiotic Resistance in an Experimental Evolution Approach
Published on: December 14, 2019
SOS-mediated prophage induction constrains resistance evolution to DNA-damaging antibiotics.
Amy D Zamora1,2,3, Shreyas V Pai1,2,3, Kepler S Mears1,2,3
1Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Bacterial prophages, when induced by antibiotics, create an evolutionary bottleneck. This leads to less frequent but higher-level antibiotic resistance by favoring specific mutations and dampening the SOS response.
Area of Science:
- Microbiology
- Evolutionary Biology
- Genetics
Background:
- Most bacteria are lysogens, carrying temperate phages (prophages) in their genomes.
- Prophages can be induced by the bacterial SOS response, triggered by DNA-damaging antibiotics, leading to host lysis.
- This prophage-antibiotic synergy sensitizes bacteria to antibiotics, but its effect on resistance evolution is unclear.
Purpose of the Study:
- To investigate how prophage induction influences the evolution of bacterial resistance to DNA-damaging antibiotics.
- To understand the genetic mechanisms underlying resistance in lysogenic bacteria selected under antibiotic pressure.
Main Methods:
- Comparative genomics and whole-genome sequencing of ciprofloxacin-resistant lysogens.
- Phenotypic analysis of bacterial sensitivity and resistance evolution under antibiotic selection.
- Assessment of the bacterial SOS response in lysogenic and non-lysogenic strains.
Main Results:
- Lysogenic bacteria selected with ciprofloxacin exhibited reduced frequency of resistance emergence but higher resistance levels.
- Whole-genome sequencing revealed mutations in drug targets, efflux pumps, and stress regulators contributing to resistance.
- Resistant lysogens showed a dampened SOS response, indicating prophage induction acts as a selective filter.
- Prophage carriage did not affect resistance evolution for antibiotics not causing DNA damage.
Conclusions:
- Prophage induction acts as an evolutionary bottleneck, restricting resistance pathways and favoring large-effect mutations.
- This process can accelerate the evolution of high-level antibiotic resistance in lysogenic bacteria.
- The findings highlight the complex interplay between phage-host dynamics and antibiotic resistance evolution.
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