ZnO/Curcumin Nanocomposites for Enhanced Inhibition of Pseudomonas aeruginosa Virulence via LasR-RhlR Quorum Sensing Systems

Abstract

The indiscriminate and excessive use of antibiotics has ultimately led to the emergence of bacterial resistant mutants or superbugs. These superbugs are difficult to control with conventional antibiotics. Disabling quorum sensing (QS), a population-density-dependent cell-to-cell communication process used by bacteria to coordinate the expression of virulence genes and biofilm formation, with dietary phytochemicals is emerging as a non-antibiotic strategy to inhibit bacterial pathogenicity. Although curcumin is an anti-QS agent and its delivery to cells has been a challenge due to poor bioavailability, ZnO/curcumin nanocomposites (ZnC-NCs) were fabricated with enhanced delivery of curcumin inside the bacterial superbug Pseudomonas aeruginosa PAO1 for effective inhibition of its QS and biofilm formation. Sustained release of curcumin from ZnC-NCs was observed where 51% curcumin at pH 7.2 and 83% curcumin at pH 5.5 were released within 48 h. ZnC-NCs also decreased the production of virulence factors and biofilm formation without affecting planktonic cell growth. Both LasR and RhlR QS systems were inhibited by ZnC-NCs. ZnC-NCs were also capable of protecting both mice as well as lung epithelial cells from killing by PAO1. The superoxide anions (O2^-1) were also found as key players in suppressing PAO1 QS systems by ZnC-NCs. Overall, ZnC-NCs enhanced curcumin bioavailability for effective inhibition of QS signaling in P. aeruginosa via LasR-RhlR suppression and O2^-1 generation.