Veratraldehyde Inhibits Motility Phenotypes and Targets Biofilm Formation of <i>Pseudomonas aeruginosa</i>: Insights From Computational and Experimental Studies

Pseudomonas aeruginosa, a versatile pathogen that poses significant challenges in healthcare and food industries due to its ability to form biofilms. The present study investigated the anti-biofilm properties of a natural compound, veratraldehyde (VD) against P. aeruginosa biofilms. Although VD exhibited weak antibacterial activity (minimum inhibitory concentration [MIC] > 512 µg/mL), it demonstrated potent motility inhibition at sub-inhibitory concentrations, with the highest inhibition observed in swimming (78.13%), twitching (70.96%), and swarming (56.74%) across various strains. Tube assay showed highest inhibition on Day 1 (32.73%) and Day 3 (15.58%) across various strains with VD. Detailed microscopic analysis (light, florescence, and scanning electron microscopy) clearly show that veratraldehyde effectively inhibits biofilm formation in multiple P. aeruginosa strains. In silico molecular docking and dynamic simulation studies suggest that veratraldehyde may target the PilY protein, a component of Type-IV pili involved in pilus biogenesis, potentially disrupting biofilm formation at a molecular level. In silico pharmacokinetic analysis such as absorption, distribution, metabolism, and excretion (ADME) analysis indicates favorable properties (e.g., bioavailability, solubility, drug likeness, high gastrointestinal (GI) absorption, and skin permeability), making veratraldehyde a promising candidate for anti-biofilm therapeutic development. These results highlight its potential as a natural alternative to conventional antibiotics in combating P. aeruginosa biofilm associated infections.