Stationary-Phase Pseudomonas aeruginosa Fluoroquinolone Persisters Mostly Avoid DNA Double-Stranded Breaks
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Abstract
When susceptible bacterial cultures are treated with antibiotics, some cells can survive treatment without heritable resistance, giving rise to susceptible daughter cells in a phenomenon termed antibiotic persistence. Current models of fluoroquinolone (FQ) persistence in stationary-phase cultures posit that post-treatment resuscitation is dependent on double-stranded break (DSB) repair through RecA-mediated homology-directed repair. Previously, we found that stationary-phase P. aeruginosa does not depend on RecA to persist. In this work, we ask whether P. aeruginosa FQ persisters from stationary-phase cultures require DSB repair at all. We measured DSB formation in Levofloxacin (LVX)-treated cells recovering from treatment using strains expressing fluorescently labeled DSB-binding protein, Gam. We find that, surprisingly, the majority of P. aeruginosa LVX persisters survive treatment without apparent DSBs. Persisters that have evidence of DSBs take longer until their first division compared to persisters without DSBs, and the phenotypes of their progeny suggest how persisters cope with DSBs—via repair or by damage sequestration—in order to successfully propagate. These observations pave the way for mechanistic studies into P. aeruginosa FQ persistence and highlight the need for single-cell tools to track FQ-induced damage.
Article activity feed
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Susan Lovett, Thalia Sass
Review 4: "Stationary-Phase Pseudomonas aeruginosa Fluoroquinolone Persisters Mostly Avoid DNA Double-Stranded Breaks"
Reviewers agree that the work provides meaningful mechanistic insight into antibiotic persistence and advances understanding of species-specific survival strategies under fluoroquinolone stress.
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Stanley Brul
Review 3: "Stationary-Phase Pseudomonas aeruginosa Fluoroquinolone Persisters Mostly Avoid DNA Double-Stranded Breaks"
Reviewers agree that the work provides meaningful mechanistic insight into antibiotic persistence and advances understanding of species-specific survival strategies under fluoroquinolone stress.
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Tobias Dörr
Review 2: "Stationary-Phase Pseudomonas aeruginosa Fluoroquinolone Persisters Mostly Avoid DNA Double-Stranded Breaks"
Reviewers agree that the work provides meaningful mechanistic insight into antibiotic persistence and advances understanding of species-specific survival strategies under fluoroquinolone stress.
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Bork Berghoff
Review 1: "Stationary-Phase Pseudomonas aeruginosa Fluoroquinolone Persisters Mostly Avoid DNA Double-Stranded Breaks"
Reviewers agree that the work provides meaningful mechanistic insight into antibiotic persistence and advances understanding of species-specific survival strategies under fluoroquinolone stress.
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Strength of evidence
Reviewers: B Berghoff (Ulm University) | 📗📗📗📗◻️
T Dörr (Cornell University) | 📒📒📒◻️◻️
S Brul (University of Amsterdam) | 📘📘📘📘📘
S Lovett & T Sass (Brandeis University) | 📘📘📘📘📘 -
