Natural Compounds as Novel Biofilm Inhibitors: Targeting Multidrug-Resistant Bacterial Pathogenesis

Introduction: Biofilm formation by multidrug-resistant (MDR) bacteria confers increased antimicrobial tolerance and contributes to persistent infections, presenting significant therapeutic challenges. These challenges have driven research into natural compounds that may target key processes, including efflux pump activity, quorum sensing, bacterial adhesion, and biofilm development. This study investigates the anti-biofilm efficacy of six naturally occurring compounds—berberine, chitosan, curcumin, eugenol, linoleic acid, and reserpine—against clinically relevant aerobic MDR bacterial pathogens. Methods: Biofilm formation was evaluated in ۲۰۰ MDR clinical isolates, including isolates of Escherichia coli (n=۴۹), Klebsiella pneumoniae (n=۴۶), Acinetobacter baumannii (n=۲۴), Pseudomonas aeruginosa (n=۲۹), Staphylococcus aureus (n=۲۵), and Staphylococcus epidermidis (n=۲۷), sourced from various clinical specimens, including pus, urine, blood, and sputum. Biofilm production was quantified using the modified tissue culture plate (MTCP) method. From these isolates, ۳۶ strong biofilm-forming isolates were selected, and the minimum biofilm inhibitory concentration (MBIC) of each compound was determined via a microtiter plate assay with two-fold serial dilutions. Results: Of ۲۰۰ isolates, ۱۰۱ (۵۰.۵%) exhibited biofilm formation. MBIC values ranged from ۰.۰۱۵۶ mg/mL (lowest for eugenol against E. coli and reserpine against E. coli, K. pneumoniae, and S. aureus) to ۱ mg/mL (for curcumin against P. aeruginosa and A. baumannii). Eugenol and reserpine showed significantly lower MBICs compared to curcumin (P < ۰.۰۵). Eugenol displayed the lowest mean MBIC (۰.۰۴۹ mg/mL) across the ۳۶ selected strong biofilm-forming isolates, followed by reserpine (۰.۰۷۰ mg/mL), while curcumin exhibited the highest mean MBIC (۰.۵۸۳ mg/mL). Linoleic acid demonstrated its lowest MBIC (۰.۰۳۱۲ mg/mL) against K. pneumoniae. Conclusion: The tested compounds exhibited variable anti-biofilm potency, with eugenol and reserpine demonstrating the greatest efficacy and curcumin the least, suggesting limited anti-biofilm efficacy at tested concentrations. These findings underscore the potential of eugenol, reserpine, linoleic acid, berberine, and chitosan as promising in vitro anti-biofilm candidates for managing biofilm-associated infections caused by MDR bacteria; however, in vivo efficacy, pharmacokinetics, and safety warrant further investigation in animal models and clinical trials.

کلیدواژه ها:

Anti-biofilm activity ، Berberine ، Biofilm ، Chitosan ، Curcumin ، Eugenol ، Linoleic acid ، Multidrug-resistant (MDR) bacteria ، Natural compounds ، Reserpine