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

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.