title: Phenazine virulence factor binding to extracellular DNA is important for Pseudomonas aeruginosa biofilm formation.
abstract: Bacterial resistance to conventional antibiotics necessitates the identification of novel leads for infection control. Interference with extracellular phenomena, such as quorum sensing, extracellular DNA integrity and redox active metabolite release, represents a new frontier to control human pathogens such as Pseudomonas aeruginosa and hence reduce mortality. Here we reveal that the extracellular redox active virulence factor pyocyanin produced by P. aeruginosa binds directly to the deoxyribose-phosphate backbone of DNA and intercalates with DNA nitrogenous base pair regions. Binding results in local perturbations of the DNA double helix structure and enhanced electron transfer along the nucleic acid polymer. Pyocyanin binding to DNA also increases DNA solution viscosity. In contrast, antioxidants interacting with DNA and pyocyanin decrease DNA solution viscosity. Biofilms deficient in pyocyanin production and biofilms lacking extracellular DNA show similar architecture indicating the interaction is important in P. aeruginosa biofilm formation.
authors: School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: Theerthankar
authors: T
authors: Das
authors: School of Chemistry, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: Samuel K
authors: SK
authors: Kutty
authors: School of Chemistry, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: Roya
authors: R
authors: Tavallaie
authors: School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: Amaye I
authors: AI
authors: Ibugo
authors: School of Chemistry, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: Janjira
authors: J
authors: Panchompoo
authors: School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: Shama
authors: S
authors: Sehar
authors: School of Chemistry, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: Leigh
authors: L
authors: Aldous
authors: Centre for Vascular Research and School of Medical Sciences, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: Amanda W S
authors: AW
authors: Yeung
authors: Centre for Vascular Research and School of Medical Sciences, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: Shane R
authors: SR
authors: Thomas
authors: School of Chemistry, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: Naresh
authors: N
authors: Kumar
authors: School of Chemistry, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: J Justin
authors: JJ
authors: Gooding
authors: School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW), Sydney 2052, Australia.
authors: Mike
authors: M
authors: Manefield
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D018441:Biofilms; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D004579:Electron Transport; D005110:Extracellular Space / Q000378:metabolism; D010084:Oxidation-Reduction; D010619:Phenazines / Q000378:metabolism*; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity / Q000502:physiology*; D011710:Pyocyanine / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics; D037521:Virulence Factors / Q000378:metabolism*; D014783:Viscosity
chemical_list: D000975:Antioxidants; D010619:Phenazines; D037521:Virulence Factors; D004247:DNA; D011710:Pyocyanine; D003850:Deoxyribonuclease I