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Updated: Jan 9, 2026

Understanding the Impact of Temperate Bacteriophages on Their Lysogens Through Transcriptomics
Published on: January 5, 2024
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.
Abstract:
Bacteriophages have proven invaluable in combatting drug-resistant bacteria. Bias towards exclusive use of obligately lytic phages has restricted the range of phage therapy, however, since at least half of all Caudovirecetes are temperate, and such phages remain the only option available for many problematic pathogens - including the notorious members of the Burkholderia cepacia complex (Bcc). Temperate phage-antibiotic synergy (tPAS), a unique strategy that leverages lysogen-forming phages as adjuvants to traditional antibiotics, has been validated for phages infecting E. coli and P. aeruginosa and is a major step towards normalization of temperate phages in therapeutics. In this report, we extend tPAS to Burkholderia phages and show that combining these phages with subinhibitory doses of ciprofloxacin overcomes natural limitations in antibacterial activity caused by lysogen formation. We further demonstrate that the magnitude of this effect correlates with the lysogenization frequencies of utilized phages, meaning tPAS is tailored specifically to otherwise ineffective, highly lysogenic phages. Finally, we observed heterogeneity in lysogen depletion rates among synergizing phages, suggesting 'complete' lysogen depletion is not required for antibacterial synergy. Our results support the use of temperate phages as synergizing adjuvants against Bcc species, thereby substantially expanding the limited arsenal of tools available for combating these pathogens.
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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