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<p>Screening plant-based alkaloids is one of the alternate therapeutic approaches to control antibiotic-resistant micro-pathogens. Our research highlighted beta carboline alkaloids as one of the most promising small molecules to established anti-virulent and anti-biofilm efficacy to regulate resistant bacterial infection. In vitro, in vivo assay and molecular docking were employed. Result Among six different bacterial strains, harmine showed 160 ± 2.07&#xa0;µg/ml as the minimum inhibitory concentrations (MIC), followed by harmalol (190 ± 2.46) and harmaline (270 ± 3.04) against <i>Staphylococcus aureus</i> 96 (SA 96). Methicillin-resistant <i>Staphylococcus aureus</i> MRSA strain also showed inhibition of growth (MIC) by harmine, harmalol and harmaline at 250 ± 3.10, 320 ± 3.39 and 390 ± 4.90&#xa0;µg/ml, respectively. MRSA is a prominent source of nosocomial infections, forming biofilms. The growth of biofilm got decreased with exposure to the sub-MIC concentrations (60, 80 and 100&#xa0;µg/mL) of harmine, suppressing protein, targeting EPS and inhibiting extracellular protease. Harmine promote biofilm cell detachment by targeting cell surface hydrophobicity. Harmine causes depolarization of bacteria’s cell membrane. Bacterial cell viability was further studied by propidium iodide (PI), DNA leakage and Acridine Orange (A/O)-Ethidium Bromide (EtBr) assay. Harmine treatment leads to increased reactive oxygen species (ROS) levels in biofilm cells. The binding affinities by molecular docking and dynamics indicated highest affinity with AgrC (-6.17&#xa0;kcal/mol). Harmine treatment (32.0&#xa0;mg/ kg bw, IP for five days) further recovered MRSA infected lungs in BALB/c mice. The findings revealed that among the three beta carboline alkaloids, harmine might be employed as a potential antibiofilm and antimicrobial agent for successful control of clinical <i>S. aureus</i> infection.</p>

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Beta Carboline Alkaloid Harmine as Biofilm Inhibitor: In vitro, in Silico and in Vivo Studies Suppressing Growth and Virulence-Related Factors Against Resistant Staphylococcus Aureus

  • 期刊论文

  • 发表日期：

    2025年12月27日

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  • Paromita Sarkar,
  • Sharmistha Das,
  • Shrabasti Bandyopadhyay,
  • Priyanka Gopi,
  • Samik Biswas,
  • Prosun Tribedi,
  • Prateek Pandya,
  • Supratim Mandal,
  • kakali bhadra

摘要

Screening plant-based alkaloids is one of the alternate therapeutic approaches to control antibiotic-resistant micro-pathogens. Our research highlighted beta carboline alkaloids as one of the most promising small molecules to established anti-virulent and anti-biofilm efficacy to regulate resistant bacterial infection. In vitro, in vivo assay and molecular docking were employed. Result Among six different bacterial strains, harmine showed 160 ± 2.07 µg/ml as the minimum inhibitory concentrations (MIC), followed by harmalol (190 ± 2.46) and harmaline (270 ± 3.04) against Staphylococcus aureus 96 (SA 96). Methicillin-resistant Staphylococcus aureus MRSA strain also showed inhibition of growth (MIC) by harmine, harmalol and harmaline at 250 ± 3.10, 320 ± 3.39 and 390 ± 4.90 µg/ml, respectively. MRSA is a prominent source of nosocomial infections, forming biofilms. The growth of biofilm got decreased with exposure to the sub-MIC concentrations (60, 80 and 100 µg/mL) of harmine, suppressing protein, targeting EPS and inhibiting extracellular protease. Harmine promote biofilm cell detachment by targeting cell surface hydrophobicity. Harmine causes depolarization of bacteria’s cell membrane. Bacterial cell viability was further studied by propidium iodide (PI), DNA leakage and Acridine Orange (A/O)-Ethidium Bromide (EtBr) assay. Harmine treatment leads to increased reactive oxygen species (ROS) levels in biofilm cells. The binding affinities by molecular docking and dynamics indicated highest affinity with AgrC (-6.17 kcal/mol). Harmine treatment (32.0 mg/ kg bw, IP for five days) further recovered MRSA infected lungs in BALB/c mice. The findings revealed that among the three beta carboline alkaloids, harmine might be employed as a potential antibiofilm and antimicrobial agent for successful control of clinical S. aureus infection.