Chitosan-Aspirin Combination Inhibits Quorum-Sensing Synthases (

BACKGROUND: Quorum sensing (QS) controls the virulence of P. aeruginosa. This study aims to determine the anti-QS activity of aspirin alone and in combination with chitosan to reach maximum inhibition. We tested ten virulent Pseudomonas aeruginosa (P. aeruginosa) isolates and screened for N-acyl homoserine lactone (AHL) production using Agrobacterium tumefaciens as a biosensor. P. aeruginosa isolates were treated with sub-minimum inhibitory concentrations (MICs) of aspirin and chitosan-aspirin. We used broth microdilution and checkerboard titration methods to determine the MICs and the synergistic effect of these two compounds, respectively. Real-time polymerase chain reaction (PCR) was used to estimate the anti-QS activity of the aspirin-chitosan combination on the expression of lasI and rhlI genes. RESULTS: Aspirin decreased the motility and production of AHLs, pyocyanin, and biofilm. Chitosan potentiated the inhibitory effect of aspirin. The chitosan-aspirin combination inhibited lasI and rhlI gene expression in PAO1 (ATCC 15692) by 7.12- and 0.92-fold, respectively. In clinical isolates, the expression of lasI and rhlI was decreased by 1.76 × 102- and 1.63 × 104-fold, respectively. Molecular docking analysis revealed that aspirin could fit into the active sites of the QS synthases lasI and rhlI with a high binding affinity, causing conformational changes that resulted in their inhibition. CONCLUSIONS: The chitosan-aspirin combination provides new insights into treating virulent and resistant P. aeruginosa.