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Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms

Costa, Kyle C. and Glasser, Nathaniel R. and Conway, Stuart J. and Newman, Dianne K. (2017) Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms. Science, 355 (6321). pp. 170-173. ISSN 0036-8075. http://resolver.caltech.edu/CaltechAUTHORS:20161208-131717229

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Abstract

The opportunistic pathogen Pseudomonas aeruginosa produces colorful redox-active metabolites called phenazines, which underpin biofilm development, virulence, and clinical outcomes. Although phenazines exist in many forms, the best studied is pyocyanin. Here, we describe pyocyanin demethylase (PodA), a hitherto uncharacterized protein that oxidizes the pyocyanin methyl group to formaldehyde and reduces the pyrazine ring via an unusual tautomerizing demethylation reaction. Treatment with PodA disrupts P. aeruginosa biofilm formation similarly to DNase, suggesting interference with the pyocyanin-dependent release of extracellular DNA into the matrix. PodA-dependent pyocyanin demethylation also restricts established biofilm aggregate populations experiencing anoxic conditions. Together, these results show that modulating extracellular redox-active metabolites can influence the fitness of a biofilm-forming microorganism.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.aag3180DOIArticle
http://science.sciencemag.org/content/355/6321/170PublisherArticle
http://www.sciencemag.org/cgi/content/full/science.aag3180/DC1PublisherSupplementary Information
ORCID:
AuthorORCID
Newman, Dianne K.0000-0003-1647-1918
Additional Information:© 2016 American Association for the Advancement of Science. 8 June 2016; resubmitted 14 October 2016. Accepted 29 November 2016. Published online 8 December 2016. The final model and native data set for PodA were submitted to the wwPDB under accession code 5K21. We thank Elena Perry, Lucas Meirelles, William DePas and Douglas Rees for assistance in experimental design and interpretation. K.C.C. was supported by a Ruth L. Kirschstein National Research Service Award from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, Grant no. F32AI112248. N.R.G. was supported by the National Science Foundation Graduate Research Fellowship, Grant no. 1144469. This work was further supported by the Howard Hughes Medical Institute (HHMI), NIH (Grant 5R01HL117328-03) and the Molecular Observatory at the Beckman Institute, California Institute of Technology through the Gordon and Betty Moore Foundation and the Sanofi-Aventis Bioengineering Research Program at Caltech Additional support was provided by the Stanford Synchrotron Radiation Lightsource, which is funded by the U.S. Department of Energy and NIH. S.J.C. thanks St Hugh’s College, Oxford for research support. Author contributions. K.C.C. and D.K.N. conceived the project. K.C.C., N.R.G., and D.K.N. designed the experiments. K.C.C. and N.R.G. performed the experiments. K.C.C., N.R.G., S.J.C., and D.K.N. analyzed and interpreted the results. K.C.C., S.J.C. and D.K.N. wrote the paper.
Funders:
Funding AgencyGrant Number
NIH Predoctoral FellowshipF32AI112248
NSF Graduate Research Fellowship1144469
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIH5R01HL117328-03
Caltech Beckman InstituteUNSPECIFIED
Gordon and Betty Moore FoundationUNSPECIFIED
Sanofi-Aventis Bioengineering Research ProgramUNSPECIFIED
Department of Energy (DOE)UNSPECIFIED
St Hugh’s College, OxfordUNSPECIFIED
Record Number:CaltechAUTHORS:20161208-131717229
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20161208-131717229
Official Citation: Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms By Kyle C. Costa, Nathaniel R. Glasser, Stuart J. Conway, Dianne K. Newman Science13 Jan 2017 : 170-173
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:72669
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:08 Dec 2016 21:30
Last Modified:24 Oct 2017 16:47

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