<p>Increased biofilm formation and efflux pumps activity are two major contributors to the antimicrobial resistance in clinical isolates of <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>). In the present study, curcumin-functionalized Fe<sub>3</sub>O<sub>4</sub> nanoparticles were synthesized and evaluated for their anti-biofilm and efflux pump inhibitory effects against <i>P. aeruginosa</i>. The nanoparticles, designated Fe<sub>3</sub>O<sub>4</sub>@SBA-3@Curcumin, were prepared via co-precipitation method followed by surface functionalization. Comprehensive physicochemical characterization was performed using thermal analysis and multiple spectroscopic techniques. The antimicrobial efficacy of Fe<sub>3</sub>O<sub>4</sub>@SBA-3@Curcumin alone and in combination with ciprofloxacin was assessed using fractional inhibitory concentration (FIC) analysis, biofilm formation assays, and pyocyanin production measurements. FT-IR spectroscopy confirmed successful curcumin functionalization without structural degradation. FE-SEM and TEM images demonstrated nanoparticle size of 52.12&#xa0;nm and 32.20&#xa0;nm, respectively. Dynamic light scattering (DLS) analysis revealed a mean particle diameter of 101.8&#xa0;nm and excellent colloidal stability, as indicated by a zeta potential of -86.8 mV. Combination therapy exhibited a synergistic effect and significantly reduced biofilm formation and pyocyanin production. Furthermore, combined treatment with Fe₃O₄@SBA-3@Curcumin and ciprofloxacin resulted in downregulation of efflux pump genes (<i>mexA</i>,<i> mexB</i>, and <i>oprM</i>) and biofilm-associated genes (<i>algD</i> and <i>pelA</i>). Molecular docking analyses predicted favorable binding interactions between curcumin and key biofilm-related proteins involved in exopolysaccharide synthesis (algD and <i>pelD</i>), as well as efflux pump components associated with antibiotic resistance (<i>mexB</i>,<i> mexA</i>, and <i>oprM</i>) in <i>P. aeruginosa</i>. Collectively, these findings support the potential role of curcumin functionalization in attenuating biofilm formation and efflux pump activity. Overall, Fe₃O₄@SBA-3 nanoparticle may serve as an effective nanocarrier for targeted drug delivery into bacterial cells.</p>

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Anti-biofilm and Efflux Pump Inhibitory Function of Fe3O4@SBA-3@Curcumin Nanoparticles on drug resistant isolates of Pseudomonas aeruginosa and Molecular Docking Analysis

  • Ali Pabousi Sadatmahale,
  • Alireza Nouhi Kararoudi,
  • Hossein Zahmatkesh,
  • Hanieh Haghdoust Kooyshahi,
  • Shahin Nezamivand Chegini,
  • Seyed Reza Garakoui,
  • Mahdi Shahriarinour,
  • Mohammad Nikpassand,
  • Najmeh Ranji

摘要

Increased biofilm formation and efflux pumps activity are two major contributors to the antimicrobial resistance in clinical isolates of Pseudomonas aeruginosa (P. aeruginosa). In the present study, curcumin-functionalized Fe3O4 nanoparticles were synthesized and evaluated for their anti-biofilm and efflux pump inhibitory effects against P. aeruginosa. The nanoparticles, designated Fe3O4@SBA-3@Curcumin, were prepared via co-precipitation method followed by surface functionalization. Comprehensive physicochemical characterization was performed using thermal analysis and multiple spectroscopic techniques. The antimicrobial efficacy of Fe3O4@SBA-3@Curcumin alone and in combination with ciprofloxacin was assessed using fractional inhibitory concentration (FIC) analysis, biofilm formation assays, and pyocyanin production measurements. FT-IR spectroscopy confirmed successful curcumin functionalization without structural degradation. FE-SEM and TEM images demonstrated nanoparticle size of 52.12 nm and 32.20 nm, respectively. Dynamic light scattering (DLS) analysis revealed a mean particle diameter of 101.8 nm and excellent colloidal stability, as indicated by a zeta potential of -86.8 mV. Combination therapy exhibited a synergistic effect and significantly reduced biofilm formation and pyocyanin production. Furthermore, combined treatment with Fe₃O₄@SBA-3@Curcumin and ciprofloxacin resulted in downregulation of efflux pump genes (mexA, mexB, and oprM) and biofilm-associated genes (algD and pelA). Molecular docking analyses predicted favorable binding interactions between curcumin and key biofilm-related proteins involved in exopolysaccharide synthesis (algD and pelD), as well as efflux pump components associated with antibiotic resistance (mexB, mexA, and oprM) in P. aeruginosa. Collectively, these findings support the potential role of curcumin functionalization in attenuating biofilm formation and efflux pump activity. Overall, Fe₃O₄@SBA-3 nanoparticle may serve as an effective nanocarrier for targeted drug delivery into bacterial cells.