Universal antibiotic tolerance arising from antibiotic-triggered accumulation of pyocyanin in Pseudomonas aeruginosa

PLoS Biol. 2019 Dec 16;17(12):e3000573. doi: 10.1371/journal.pbio.3000573. eCollection 2019 Dec.

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that often infects open wounds or patients with cystic fibrosis. Once established, P. aeruginosa infections are notoriously difficult to eradicate. This difficulty is in part due to the ability of P. aeruginosa to tolerate antibiotic treatment at the individual-cell level or through collective behaviors. Here, we describe a new phenomenon by which P. aeruginosa tolerates antibiotic treatment. In particular, treatment of P. aeruginosa with sublethal concentrations of antibiotics covering all major classes promoted accumulation of the redox-sensitive phenazine pyocyanin (PYO). PYO in turn conferred general tolerance against diverse antibiotics for both P. aeruginosa and other gram-negative and gram-positive bacteria. This property is shared by other redox-active phenazines produced by P. aeruginosa. Our discovery sheds new insights into the physiological functions of phenazines and has implications for designing effective antibiotic treatment protocols.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Drug Tolerance / immunology*
  • Humans
  • Immune Tolerance
  • Oxidation-Reduction
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / immunology
  • Pseudomonas aeruginosa / immunology*
  • Pseudomonas aeruginosa / metabolism
  • Pyocyanine / immunology*
  • Pyocyanine / metabolism

Substances

  • Anti-Bacterial Agents
  • Pyocyanine