title: Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms.
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.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Costa
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Nathaniel R
authors.initials: NR
authors.lastname: Glasser
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Conway
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. dkn@caltech.edu.|Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Dianne K
authors.initials: DK
authors.lastname: Newman
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D008745:Methylation; D019907:Mycobacterium fortuitum / Q000201:enzymology*; D010084:Oxidation-Reduction; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry* / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D011710:Pyocyanine / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D004247:DNA; D011710:Pyocyanine; D010089:Oxidoreductases, N-Demethylating