Abstract
Quorum sensing (QS) plays an important role during infection for the opportunistic human pathogen Pseudomonas aeruginosa. Quorum sensing inhibition (QSI) can disrupt this initial event of infection without killing bacterial cells, and thus QS inhibitors have been suggested as novel approaches for anti-infective therapy. Cinnamaldehyde (CAD) is a P. aeruginosa biofilm inhibitor and disperser of preformed biofilms. In this study, the combined use of CAD and colistin (COL) revealed a synergistic activity, but this was not the case for CAD combined with carbenicillin, tobramycin (TOB), or erythromycin in checkerboard assays for P. aeruginosa. CAD demonstrated QSI activity by repression of the expression of lasB, rhlA and pqsA in GFP reporter assays. Approximately 70% reduction in GFP production was observed with the highest CAD concentration tested in all the QS reporter strains. TOB also showed strong QSI when combined with CAD in reporter assays. Combination treatments revealed an additive activity of CAD with COL and TOB in biofilm inhibition (75.2% and 83.9%, respectively) and preformed biofilm dispersion (~90% for both) when compared to the individual treatments. Therefore, a proposed method to mitigate P. aeruginosa infection is a combination therapy of CAD with COL or CAD with TOB as alternatives to current individual drug therapies.