Synergy between ciprofloxacin and temperate phages overcomes therapeutic limitations caused by lysogen formation

P Lauman1,2, T R H Cassell1, J J Dennis3

  • 1University of Alberta, Edmonton, Canada.

Scientific Reports
|December 4, 2025
PubMed

Insights

Temperate phages, combined with antibiotics, show promise against drug-resistant Burkholderia cepacia complex (Bcc) bacteria. This phage-antibiotic synergy strategy effectively overcomes limitations posed by lysogen formation in Bcc infections.

Area of Science:

  • Microbiology
  • Bacteriophage Therapy
  • Antimicrobial Resistance

Background:

  • Bacteriophages are crucial for combating drug-resistant bacteria.
  • The therapeutic potential of temperate phages, which form lysogens, has been underexplored.
  • Temperate phage-antibiotic synergy (tPAS) has been validated for E. coli and P. aeruginosa.

Purpose of the Study:

  • To investigate the efficacy of tPAS using temperate phages against Burkholderia cepacia complex (Bcc) pathogens.
  • To determine if tPAS can overcome antibacterial limitations caused by lysogen formation in Bcc species.
  • To explore the relationship between lysogenization frequency and synergistic antibacterial effects.

Main Methods:

  • Utilized temperate phages infecting Bcc species in combination with subinhibitory doses of ciprofloxacin.
  • Assessed the antibacterial activity and lysogen formation of phage-antibiotic combinations.
  • Quantified lysogenization frequencies and lysogen depletion rates.

Main Results:

  • Temperate phage-ciprofloxacin combinations demonstrated synergistic antibacterial activity against Bcc species.
  • The magnitude of synergy correlated with the lysogenization frequencies of the phages used.
  • Observed heterogeneity in lysogen depletion, indicating complete depletion is not essential for synergy.

Conclusions:

  • Temperate phages can be effectively employed as synergizing adjuvants with antibiotics against Bcc pathogens.
  • tPAS significantly expands therapeutic options for combating challenging Bcc infections.
  • The findings support the broader integration of temperate phages into therapeutic strategies.

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