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Both toxic and beneficial effects of pyocyanin contribute to the lifecycle of Pseudomonas aeruginosa

Meirelles, Lucas A. and Newman, Dianne K. (2018) Both toxic and beneficial effects of pyocyanin contribute to the lifecycle of Pseudomonas aeruginosa. Molecular Microbiology, 110 (6). pp. 995-1010. ISSN 0950-382X. PMCID PMC6281804. doi:10.1111/mmi.14132.

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Pseudomonas aeruginosa, an opportunistic pathogen, produces redox‐active pigments called phenazines. Pyocyanin (PYO, the blue phenazine) plays an important role during biofilm development. Paradoxically, PYO auto‐poisoning can stimulate cell death and release of extracellular DNA (eDNA), yet PYO can also promote survival within biofilms when cells are oxidant‐limited. Here, we identify the environmental and physiological conditions in planktonic culture that promote PYO‐mediated cell death. We demonstrate that PYO auto‐poisoning is enhanced when cells are starved for carbon. In the presence of PYO, cells activate a set of genes involved in energy‐dependent defenses, including: (i) the oxidative stress response, (ii) RND efflux systems and (iii) iron‐sulfur cluster biogenesis factors. P. aeruginosa can avoid PYO poisoning when reduced carbon is available, but blockage of adenosine triphosphate (ATP) synthesis either through carbon limitation or direct inhibition of the F_0F_1‐ATP synthase triggers death and eDNA release. Finally, even though PYO is toxic to the majority of the population when cells are nutrient limited, a subset of cells is intrinsically PYO resistant. The effect of PYO on the producer population thus appears to be dynamic, playing dramatically different yet predictable roles throughout distinct stages of growth, helping rationalize its multifaceted contributions to biofilm development.

Item Type:Article
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URLURL TypeDescription CentralArticle
Meirelles, Lucas A.0000-0003-3194-7136
Newman, Dianne K.0000-0003-1647-1918
Additional Information:© 2018 John Wiley & Sons Ltd. Issue Online: 05 December 2018; Version of Record online: 23 October 2018; Accepted manuscript online: 19 September 2018; Manuscript accepted: 14 September 2018. We thank all the members of the Newman lab for experimental advice and feedback on the manuscript; Megan Bergkessel was particularly generous with her time and intellectual support. We also thank Scott Saunders for helping with pyocyanin quantification. Grants to D.K.N. from the ARO (W911NF‐17‐1‐0024) and NIH 341 (1R01AI127850‐01A1) supported this research.
Funding AgencyGrant Number
Army Research Office (ARO)W911NF-17-1-0024
Issue or Number:6
PubMed Central ID:PMC6281804
Record Number:CaltechAUTHORS:20180924-131756393
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Official Citation:Meirelles, L. A. and Newman, D. K. (2018), Both toxic and beneficial effects of pyocyanin contribute to the lifecycle of Pseudomonas aeruginosa. Mol Microbiol, 110: 995-1010. doi:10.1111/mmi.14132
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:89888
Deposited By: Tony Diaz
Deposited On:24 Sep 2018 23:06
Last Modified:16 Feb 2022 23:28

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