Chlorhexidine's potential in inhibiting Pseudomonas aeruginosa biofilm formation: A reverse docking study on quorum sensing proteins

Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa poses a significant clinical challenge due to its robust biofilm
formation and resistance mechanisms. Chlorhexidine (CHX), an antiseptic agent, has shown potential in inhibiting biofilm formation,
though its mechanism is not fully understood. To elucidate the mechanism of action and potential of chlorhexidine in mitigating biofilm
formation, we conducted reverse docking analyses targeting key quorum-sensing proteins in P. aeruginosa. Protein structures of six
quorum sensing and biofilm proteins were obtained from the Protein Data Bank. The structure of CHX was retrieved from PubChem
and prepared for docking. Potential binding pockets in the protein structures were identified using Fpocket, and docking simulations
were performed with SMINA. We generated 395 docking poses across all proteins. The highest binding affinity was observed at PslG.
Additionally, CHX's high binding affinities with RhlR and LasR indicate its potential to interfere with quorum sensing pathways. CHX
shows strong binding affinities to key quorum-sensing proteins, particularly PslG, RhlR, and LasR. This suggests CHX could disrupt
biofilm formation and quorum sensing in P. aeruginosa.