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Updated: Dec 20, 2025

Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi
Published on: September 28, 2022
Adapting a Phage to Combat Phage Resistance.
Elina Laanto1,2, Kati Mäkelä2, Ville Hoikkala2
1Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Programme, University of Helsinki, 00014 Helsinki, Finland.
Bacterial resistance to phage therapy is a challenge, but experimental phage adaptation can overcome it. Evolved phages regained infectivity against resistant bacteria but showed reduced adsorption, highlighting a trade-off in phage therapy development.
Area of Science:
- Microbiology
- Bacteriology
- Virology
- Genetics
Background:
- Antibiotic resistance necessitates alternative treatments like phage therapy.
- Bacterial resistance to bacteriophages (phages) can limit treatment efficacy.
- Experimental phage adaptation aims to restore infectivity against resistant hosts.
Purpose of the Study:
- To investigate phage-host interactions and bacterial resistance evolution.
- To adapt a myophage (FCV-1) to overcome resistance in *Flavobacterium columnare*.
- To characterize trade-offs in phage infectivity and host range after adaptation.
Main Methods:
- Co-culturing of myophage FCV-1 with *Flavobacterium columnare* in lake water.
- Isolation and characterization of resistant bacterial clones and adapted phage isolates.
- Phage genome sequencing to identify mutations responsible for regained infectivity.
- Measurement of phage adsorption rates to assess infectivity trade-offs.
Main Results:
- Rapid emergence of phage resistance in *F. columnare* isolates (16/18) within one day.
- Identified surface modification and CRISPR-Cas as bacterial resistance mechanisms.
- An adapted phage isolate regained infectivity against 18/32 resistant clones.
- Mutations in putative tail genes of the evolved phage were identified.
- The adapted phage exhibited significantly lower adsorption rates than the ancestral phage.
Conclusions:
- Bacterial resistance to phage therapy evolves rapidly through various mechanisms.
- Experimental phage adaptation can restore efficacy against resistant bacterial strains.
- Phage adaptation involves trade-offs, such as reduced adsorption, impacting overall effectiveness.
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