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Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi
Published on: September 28, 2022
Phage-Antibiotic Synergy (PAS): beta-lactam and quinolone antibiotics stimulate virulent phage growth
André M Comeau1, Françoise Tétart, Sabrina N Trojet
1Laboratoire de Microbiologie et Génétique Moléculaires, Centre National de la Recherche Scientifique, Université Paul Sabatier-Toulouse, Toulouse, France.
Abstract:
Although the multiplication of bacteriophages (phages) has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage PhiMFP by more than 7-fold. We name this phenomenon Phage-Antibiotic Synergy (PAS). A related effect was observed in diverse host-phage systems, including the T4-like phages, with beta-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages.
Insights
Sub-lethal antibiotic concentrations can significantly boost virulent bacteriophage (phage) production in host bacteria. This Phage-Antibiotic Synergy (PAS) phenomenon is linked to bacterial cell filamentation, not the SOS response.
Area of Science:
- Microbiology
- Bacteriology
- Virology
Background:
- Bacteriophage (phage) multiplication significantly impacts the biosphere.
- Environmental factors influencing phage production are not well understood.
Purpose of the Study:
- To investigate the effect of sub-lethal antibiotic concentrations on phage production.
- To characterize the phenomenon of Phage-Antibiotic Synergy (PAS).
Main Methods:
- Utilized uropathogenic Escherichia coli and phage PhiMFP to study antibiotic effects.
- Tested diverse host-phage systems with various antibiotics (beta-lactam, quinolone) and mitomycin C.
- Examined the role of bacterial SOS and filamentation responses in PAS.
Main Results:
- Sub-lethal cefotaxime increased E. coli's PhiMFP production over 7-fold.
- PAS was observed across diverse phage systems, linked to antibiotics inhibiting cell division.
- The PAS effect is SOS-independent and primarily driven by cellular filamentation.
Conclusions:
- Phage-Antibiotic Synergy (PAS) is a newly identified phenomenon where antibiotics stimulate phage production.
- Cellular filamentation, induced by certain antibiotics, is the key mechanism driving PAS.
- The widespread occurrence of PAS suggests a general advantage conferred to phages.
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