[Source: PLOS Biology, full page: (LINK). Abstract, edited.]
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Universal antibiotic tolerance arising from antibiotic-triggered accumulation of pyocyanin in Pseudomonas aeruginosa
Kui Zhu, Shang Chen, Tatyana A. Sysoeva, Lingchong You
Published: December 16, 2019 / DOI: https://doi.org/10.1371/journal.pbio.3000573 / This is an uncorrected proof.
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.
Citation: Zhu K, Chen S, Sysoeva TA, You L (2019) Universal antibiotic tolerance arising from antibiotic-triggered accumulation of pyocyanin in Pseudomonas aeruginosa. PLoS Biol 17(12): e3000573. https://doi.org/10.1371/journal.pbio.3000573
Academic Editor: Nathalie Balaban, Hebrew University, ISRAEL
Received: November 1, 2018; Accepted: December 2, 2019; Published: December 16, 2019
Copyright: © 2019 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The work was partially supported by the National Key Research and Development Program of China (KZ, 2017YFC1600305), National Natural Science Foundation of China (21861142006, KZ), NIH (LY, R01GM098642) and a David and Lucile Packard Fellowship (LY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: A600 nm, absorbance 600 nm; ATCC, American Type Culture Collection; BHI, brain-heart infusion; CLSI, Clinical and Laboratory Standards Institute; ESBL, extended-spectrum beta-lactamase; Kan, kanamycin; LB, Luria-Bertani; MIC, minimum inhibitory concentration; PYO, pyocyanin; QS, quorum sensing; ROS, reactive oxygen species
Keywords: Antibiotics; Drugs Resistance; Pseudomon