Related Experiment Video
Updated: Jul 16, 2026
05:08
A Practical Guide to Phage- and Robotics-Assisted Near-Continuous Evolution
Published on: January 12, 2024
Combining Evolutionary Steering and Coevolutionary Phage Training to Generate Predictable Phage-Antibiotic Synergy
Nehme Lahoud1, Sweetzel D Labador1, Mrudula Sane1
1Ecology, Behavior and Evolution Department, University of California San Diego, San Diego, CA, 92093, USA.
Npj Antimicrobials and Resistance
|July 14, 2026
Summary
Bacteriophage therapy is promising against resistant bacteria. Training phages can make bacteria sensitive to antibiotics, enhancing treatment effectiveness through predictable coevolutionary strategies.
Area of Science:
- Microbiology
- Evolutionary Biology
- Drug Discovery
Background:
- Multidrug-resistant bacterial pathogens pose a significant global health threat.
- Bacteriophage therapy offers an alternative but faces challenges due to rapidly evolving bacterial resistance.
- Two strategies, phage training and phage-antibiotic synergy, aim to overcome resistance.
Purpose of the Study:
- To investigate the intersection of phage training and phage-antibiotic synergy.
- To determine if phage training can induce collateral sensitivity to antibiotics.
- To explore how mechanistic insights can guide predictive therapeutic design.
Main Methods:
- Utilized Escherichia coli and bacteriophage λ model system.
- Applied coevolutionary phage training and assessed bacterial resistance/sensitivity profiles.
- Investigated genetic mechanisms underlying observed sensitivities, focusing on lipopolysaccharide biosynthesis genes.
- Predicted and validated collateral sensitivity with additional antibiotics based on mechanistic understanding.
Main Results:
- Resistance to trained phage, but not untrained phage, induced collateral sensitivity to erythromycin and rifampicin in E. coli.
- This training-induced synergy was mechanistically linked to disruption of the lpcA gene.
- Successfully predicted collateral sensitivity to novobiocin and rifapentine.
- Incorporating sub-lethal erythromycin during phage training enhanced bacterial suppression by promoting phage host receptor switching.
Conclusions:
- Phage-bacteria coevolutionary outcomes can be anticipated and directed.
- Evolution-informed strategies integrating phage training and antibiotic synergy show promise for novel therapeutic design.
- This research highlights the potential of predictive, evolution-guided approaches for combating bacterial resistance.
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