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Phage-Antibiotic Synergy via Delayed Lysis.
Minjin Kim1, Yunyeol Jo1, Yoon Jung Hwang1
1Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, Gyunggi-Do, South Korea.
Applied and Environmental Microbiology
|September 16, 2018
Summary
Phage-antibiotic synergy (PAS) increases phage production when bacteria are exposed to antibiotics. This occurs because antibiotics delay bacterial lysis, allowing more time for phage assembly and release.
Area of Science:
- Microbiology
- Bacteriology
- Virology
Background:
- Phage-antibiotic synergy (PAS) describes enhanced phage production in bacteria treated with antibiotics.
- The underlying mechanisms of PAS remain incompletely understood despite a decade of observation.
Purpose of the Study:
- To investigate the mechanism of PAS across diverse bacterium-phage-antibiotic combinations.
- To determine the impact of different antibiotic classes and bacterial stress responses on PAS.
Main Methods:
- Tested PAS with various Gram-positive and Gram-negative bacteria, phages, and antibiotic classes.
- Analyzed bacterial morphology changes (filamentation/swelling) and phage production.
- Investigated phage adsorption, DNA/mRNA production, and lysis timing.
Main Results:
- PAS was observed across multiple bacterium-phage-antibiotic pairings, including with β-lactams and quinolones.
- Antibiotic-induced bacterial filamentation correlated with increased phage production.
- PAS resulted from delayed lysis due to a holin shortage in enlarged bacterial cells.
Conclusions:
- PAS is driven by delayed bacterial lysis, not increased phage adsorption or protein synthesis.
- A relative deficiency of holins in antibiotic-stressed, filamented bacteria prolongs phage particle assembly.
- Reactive oxygen species also induce PAS, suggesting a broader stress response mechanism.
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