Exploring cinnamic acid's function in reducing the quorum sensing and biofilm formation in Pseudomonas aeruginosa: in vitro and in silico investigations.

Antimicrobial resistance (AMR) has become serious global threat to the public health which is estimated to be responsible for over one million annual deaths. AMR occurs when microbes develop defence mechanism against the antibiotics. Pseudomonas aeruginosa is an opportunistic pathogen which is known to cause many infections, and it has developed resistance to multiple antibiotic classes. The continuous exposure of antibiotics imposes the risk of AMR development. In this case, targeting quorum sensing (QS) and biofilms becomes more reasonable. This study assessed the effect of cinnamic acid (CA) on biofilm formation and QS-regulated virulence factors in P. aeruginosa PAO1. Preliminary assays showed that CA inhibited violacein production by 63.88 ± 2.44% in C. violaceum 12472. The virulence factors of P. aeruginosa PAO1, namely pyocyanin production, pyoverdin production, elastase, exoprotease, rhamnolipid production, and swimming motility was reduced by 72.55 ± 4.05%, 58.90 ± 3.15%, 47.50 ± 5.55%, 65.86 ± 2.65%, 51.37 ± 2.43%, and 85.61 ± 2.52%, respectively. CA inhibited biofilm by > 65% and also reduced the bacterial colonization and aggregation. Molecular docking revealed that CA binds at the active site of target proteins of P. aeruginosa such as LasA, LasI, LasR, and PqsR. Molecular simulations validated the stability of complexes of these proteins with CA. The interaction of CA to these proteins was mainly favoured by van der Waals and electrostatic forces. This study shows CA's potential to interfere with QS and biofilm in P. aeruginosa, indicating its potential as a candidate molecule for developing new treatments aimed at targeting biofilm-associated infections.