Proanthocyanidins inhibit methicillin-resistant Staphylococcus aureus by disrupting membrane integrity and

Jingge Wang1, Xiaohui Chen2, Junpeng Huang1

  • 1College of Animal Science and Technology, Ningxia University, Yinchuan, Ningxia, 750021, China.

Insights

Proanthocyanidins (PACs) show antimicrobial effects against methicillin-resistant Staphylococcus aureus (MRSA) by disrupting cell membranes and inducing oxidative stress. These natural compounds also modulate antibiotic resistance and virulence pathways, offering potential as natural antimicrobials.

Area of Science:

  • Microbiology
  • Natural Products Chemistry
  • Molecular Biology

Background:

  • Proanthocyanidins (PACs) are recognized for their broad-spectrum antimicrobial properties and safety.
  • The precise mechanisms by which PACs combat methicillin-resistant Staphylococcus aureus (MRSA) are not fully understood.

Purpose of the Study:

  • To comprehensively investigate the antibacterial effects of PACs against MRSA.
  • To elucidate the molecular mechanisms underlying PACs' anti-MRSA activity.

Main Methods:

  • Microbiological assays, membrane integrity, and oxidative stress analyses were employed.
  • Transcriptomic profiling, RT-qPCR, molecular docking, and SPR validation were utilized.
  • Protein expression analysis and rescue experiments with antioxidants were performed.

Main Results:

  • PACs inhibited MRSA growth, disrupted membrane integrity, and induced oxidative stress.
  • Gene expression analysis revealed modulation of fatty-acid biosynthesis, oxidative stress, antibiotic resistance, and virulence pathways.
  • PACs reduced mecA expression, PBP2a, SarA, and MgrA protein levels, and enhanced susceptibility to beta-lactam antibiotics, with direct interaction with SarA confirmed.

Conclusions:

  • PACs exhibit multi-faceted anti-MRSA activity via membrane disruption and oxidative stress induction.
  • PACs modulate key resistance and virulence pathways in MRSA.
  • PACs represent a promising natural antimicrobial agent or adjuvant for MRSA infection control.

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