Computational and Experimental Validation of Aloe Vera Against Pseudomonas Aeruginosa PsrA in Interventive Antibacterial Therapeutics ^†

Background: Pseudomonas aeruginosa, a multidrug-resistant pathogen, employs biofilm formation as a key virulence strategy, complicating treatment. Pseudomonas sigma regulator A (PsrA) plays a crucial role in biofilm regulation and antimicrobial resistance. Natural compounds, such as Aloe vera metabolites, have emerged as promising alternatives for biofilm modulation. This study investigates the computational and experimental validation of Aloe vera metabolites as modulators of PsrA, potentially disrupting biofilm formation and enhancing antibacterial efficacy against P. aeruginosa. Objective: This study aims to identify and validate bioactive compounds from Aloe vera with strong binding affinity against the Pseudomonas aeruginosa PsrA protein through molecular docking, molecular dynamics and in vitro assays, with the goal of exploring potential antibacterial agents to combat resistant infections. Methods: Sequential solvent extraction using hexane, ethyl acetate and methanol was conducted to extract Aloe vera metabolites. The Aloe metabolites were then characterized using high-performance liquid chromatography (HPLC) mass spectrometry. Molecular docking and molecular dynamics simulations assessed metabolite interactions with PsrA. Antibiofilm activity was evaluated through in vitro assays, while bacterial growth inhibition was determined using minimum inhibitory concentration (MIC) assays. Results: Computational analysis identified key Aloe vera metabolites with high binding affinities for PsrA, indicating potential regulatory effects. HPLC profiling confirmed the presence of bioactive compounds. In vitro assays demonstrated significant biofilm inhibition. Conclusion: This study provides computational and experimental evidence that Aloe vera metabolites can modulate PsrA, disrupting biofilm formation in P. aeruginosa. These findings support the potential of Aloe vera-derived compounds as supplementary antibiofilm agents in combating antimicrobial resistance. Further investigations on their clinical applications are warranted.