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.
Highlights
Bacterial resistance to conventional antibiotics necessitates the identification of novel leads for infection control
This study reveals that the phenazine pyocyanin, produced by the opportunistic human pathogen P. aeruginosa, binds to DNA, resulting in increased electron transfer and structural perturbations that result in increased DNA solution viscosity
P. aeruginosa has been comprehensively investigated with respect to its pathogenicity, metabolite production, biofilm formation and extracellular DNA (eDNA) release[1,2,3,4,7,9,33]
Summary
Bacterial resistance to conventional antibiotics necessitates the identification of novel leads for infection control. W ith the rapid emergence of resistance to conventional antibiotic therapies, there exists a need to identify new targets for the control of bacterial infection Such leads are emerging as our understanding of extracellular biofilm matrices and secondary metabolite chemistry improves[1]. Major advances in bacterial biofilm biology have highlighted intercellular signaling (quorum sensing), release of extracellular DNA (eDNA) and production of electrochemically active metabolites (electron shuttles) as key behaviors dictating progression of infection[1,2,3]. Pyocyanin was shown to facilitate eDNA binding to P. aeruginosa cell surfaces to affect cellular aggregation[20]. While this implies a direct interaction between DNA and pyocyanin, to date, this hypothesis has not been presented or tested. The DNA-pyocyanin interaction is clearly a major molecular feature of P. aeruginosa biofilm behavior
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