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The Synergistic Antimicrobial Effect and Mechanism of Nisin and Oxacillin against Methicillin-Resistant

Jun Wang1,2, Xinxin Ma1, Jing Li1

  • 1School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.

International Journal of Molecular Sciences
|April 13, 2023
PubMed

Insights

Nisin (NIS) combined with Oxacillin (OX) effectively combats antibiotic-resistant MRSA infections. This combination restores antibiotic sensitivity and reduces bacterial damage in vivo.

Area of Science:

  • Microbiology
  • Pharmacology
  • Biochemistry

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) presents a significant challenge due to multi-drug resistance.
  • Novel therapeutic strategies are crucial for overcoming MRSA infections.
  • Nisin (NIS), a bacteriocin, shows potential as an antimicrobial agent.

Purpose of the Study:

  • To evaluate the synergistic antimicrobial effects of Nisin (NIS) and Oxacillin (OX) against MRSA.
  • To elucidate the underlying mechanisms of the synergistic action.
  • To assess the efficacy of the combination therapy in a murine skin infection model.

Main Methods:

  • Minimal Inhibitory Concentration (MIC) assays, checkerboard analysis, and time-kill curves were employed.
  • Biofilm formation, bacterial cell integrity (SEM/TEM), and intracellular activity were assessed.
  • Gene transcription of mecA and in vivo efficacy in mice models were analyzed.

Main Results:

  • Nisin (NIS) restored MRSA sensitivity to Oxacillin (OX) and inhibited biofilm production.
  • The combination therapy (OX + NIS) induced MRSA cell deformation and reduced infection severity in vivo.
  • NIS appeared to enhance OX sensitivity by downregulating mecA gene transcription.

Conclusions:

  • The combination of Nisin (NIS) and Oxacillin (OX) exhibits synergistic antimicrobial activity against MRSA.
  • This combination therapy offers a promising strategy for managing MRSA infections.
  • Nisin's potential to restore antibiotic sensitivity warrants further development as an anti-MRSA biomaterial.
Keywords:
in vitroin vivomethicillin resistant Staphylococcus aureusnisinoxacillinsynergistic antimicrobial effect

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