Role of Pyocyanin and Extracellular DNA in Facilitating Pseudomonas aeruginosa Biofilm Formation

Abstract

tPseudomonas aeruginosa is an opportunistic Gram‐negative bacterium that is primarilyresponsible for infections related to cystic fibrosis (CF) airways, burn wounds, urinarytract infections, surgery‐associated infections, and HIV‐related illness. Pyocyanin andextracellular DNA (eDNA) are the major factors dictating the progression of biofilmformation and infection. Pyocyanin is a potent virulence factor causing cell death ininfected CF patients and is associated with high mortality. eDNA is a key player in P.aeruginosa biofilm formation and is also responsible for the high viscosity of CF sputumthat blocks the respiratory airway passages. In this chapter, we summarize our recentfindings on the role of pyocyanin in facilitating P. aeruginosa biofilm formation.Pyocyanin promotes eDNA release in P. aeruginosa by inducing cell lysis mediated viahydrogen peroxide (H2O2) production. Pyocyanin intercalates with the nitrogenousbases of DNA and creates structural perturbation on the double‐helix structure.Pyocyanin‐eDNA binding significantly influences P. aeruginosa cell surface hydropho‐bicity and influences the physicochemical interactions facilitating bacterial cell‐to‐cellinteraction (aggregation) and ultimately facilitates robust biofilm formation. Apyocyanin knockout (ΔphzA‐G) mutant is shown to have significantly reduced eDNArelease and biofilm formation in comparison to its wild‐type. To this end, we discoverthat antioxidant glutathione directly binds to pyocyanin and modulates pyocyaninstructure and function, thus inhibiting pyocyanin‐eDNA binding and consequentlyhampering biofilm development