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Antibiotic-persistent bacterial cells exhibiting low-level ROS are eradicated by ROS-independent membrane disruption.

Yanghui Ye1, Yuanqing Tian1, Mingxin Duan1

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Summary
This summary is machine-generated.

Bacterial persister cells, which survive antibiotics by suppressing reactive oxygen species (ROS), can be eradicated by a synergistic combination of aminoglycosides and polymyxins. This ROS-independent strategy is effective against various bacteria, including those in biofilms.

Keywords:
antibioticcell deathmembrane damagepersistencereactive oxygen speciestolerance

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Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Antimicrobial Resistance

Background:

  • Bacterial persistence and tolerance contribute to treatment failure and antibiotic resistance.
  • Mechanisms of persistence and methods for eliminating persister cells remain largely unknown.
  • Understanding these mechanisms is crucial for developing effective therapies.

Purpose of the Study:

  • To identify anti-death mechanisms in *Escherichia coli* persister and tolerant cells.
  • To investigate strategies for rapid eradication of bacterial persister cells.
  • To differentiate between phenotypic tolerance and true persistence.

Main Methods:

  • Examined genetic and environmental perturbations in *E. coli*.
  • Assessed cell survival under antibiotic treatment with nutrient restoration.
  • Utilized synergistic combinations of aminoglycosides and polymyxins for bacterial killing.
  • Tested efficacy against laboratory strains, clinical isolates, biofilms, and *Staphylococcus aureus*.

Main Results:

  • Both persistent and tolerant cells suppressed reactive oxygen species (ROS) accumulation, DNA breakage, and metabolic activity.
  • Nutrient restoration killed tolerant cells but not persister cells.
  • Aminoglycoside-polymyxin combinations rapidly eradicated persister cells independently of ROS.
  • The combination demonstrated broad efficacy against Gram-negative bacteria, biofilms, and *S. aureus*.

Conclusions:

  • Suppression of ROS is a common feature of bacterial persistence and tolerance.
  • ROS-independent strategies, like aminoglycoside-polymyxin combinations, are promising for eradicating persister cells.
  • This combination offers potential for treating infections caused by diverse bacterial pathogens, including those in biofilms and Gram-positive bacteria.