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.
Highlights
Past efforts on antibiotic resistance have focused on responses of individual cells, such as mutations in the antibiotic targets, enzymatic activity that inactivates antibiotics, and increase
The ability to survive antibiotic treatment is typically considered an intrinsic property of the single bacterial cells or bacterial populations, before antibiotics are applied. In contrast to these prevailing views, here we describe a previously unknown phenomenon of collective antibiotic tolerance in Pseudomonas aeruginosa, whereby bacterial growth under subinhibitory concentrations of antibiotics is promoted by certain phenazines
We first observed that subinhibitory concentrations of kanamycin (Kan), a commonly used aminoglycoside antibiotic, induced a blue-greenish color change in P. aeruginosa PAO1 (American Type Culture Collection [ATCC] 47085) cultures
Summary
Past efforts on antibiotic resistance have focused on responses of individual cells, such as mutations in the antibiotic targets, enzymatic activity that inactivates antibiotics, and increase. We first observed that subinhibitory concentrations of kanamycin (Kan), a commonly used aminoglycoside antibiotic, induced a blue-greenish color change in P. aeruginosa PAO1 (American Type Culture Collection [ATCC] 47085) cultures. The PA14 strain, which is known to produce more PYO than PAO1 [17], exhibited qualitatively the same responses to these antibiotics (S1B Fig).
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