title: Serratia Secondary Metabolite Prodigiosin Inhibits Pseudomonas aeruginosa Biofilm Development by Producing Reactive Oxygen Species that Damage Biological Molecules.
abstract: Prodigiosin is a heterocyclic bacterial secondary metabolite belonging to the class of tripyrrole compounds, synthesized by various types of bacteria including Serratia species. Prodigiosin has been the subject of intense research over the last decade for its ability to induce apoptosis in several cancer cell lines. Reports suggest that prodigiosin promotes oxidative damage to double-stranded DNA (dsDNA) in the presence of copper ions and consequently leads to inhibition of cell-cycle progression and cell death. However, prodigiosin has not been previously implicated in biofilm inhibition. In this study, the link between prodigiosin and biofilm inhibition through the production of redox active metabolites is presented. Our study showed that prodigiosin (500 μM) (extracted from Serratia marcescens culture) and a prodigiosin/copper(II) (100 μM each) complex have strong RNA and dsDNA cleaving properties while they have no pronounced effect on protein. Results support a role for oxidative damage to biomolecules by H2O2 and hydroxyl radical generation. Further, it was demonstrated that reactive oxygen species scavengers significantly reduced the DNA and RNA cleaving property of prodigiosin. P. aeruginosa cell surface hydrophobicity and biofilm integrity were significantly altered due to the cleavage of nucleic acids by prodigiosin or the prodigiosin/copper(II) complex. In addition, prodigiosin also facilitated the bactericidal activity. The ability of prodigiosinto cause nucleic acid degradation offers novel opportunities to interfere with extracellular DNA dependent bacterial biofilms.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales Sydney, NSW, Australia.
authors.forename: Önder
authors.initials: Ö
authors.lastname: Kimyon
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South WalesSydney, NSW, Australia; Department of Infectious Diseases and Immunology, Sydney Medical School, The University of SydneySydney, NSW, Australia.
authors.forename: Theerthankar
authors.initials: T
authors.lastname: Das
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales Sydney, NSW, Australia.
authors.forename: Amaye I
authors.initials: AI
authors.lastname: Ibugo
authors.affiliation: School of Chemistry, The University of New South Wales Sydney, NSW, Australia.
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Kutty
authors.affiliation: School of Chemistry, The University of New South Wales Sydney, NSW, Australia.
authors.forename: Kitty K
authors.initials: KK
authors.lastname: Ho
authors.affiliation: Ecological Chemistry, Alfred Wegener Institute for Polar and Marine Research Institute Bremerhaven, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Tebben
authors.affiliation: School of Chemistry, The University of New South Wales Sydney, NSW, Australia.
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales Sydney, NSW, Australia.
authors.forename: Mike
authors.initials: M
authors.lastname: Manefield
keywords: Pseudomonas aeruginosa; biofilm inhibition; extracellular DNA; prodigiosin; reactive oxygen species