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Keywords:

  • artonin I;
  • cell membrane depolarization;
  • combination therapy;
  • efflux pump inhibitor;
  • flavonoid;
  • Morus mesozygiya Stapf.;
  • multidrug-resistant Staphylococcus aureus;
  • reactive oxygen species;
  • reversal of multidrug resistance

Abstract

Aims

The emergence of multidrug-resistant (MDR) Staphylococcus aureus is a challenge for the treatment of infections. We report here the antimicrobial activity of artonin I against MDR Staph. aureus, its mechanism of reversal of resistance and synergistic effects by combinational therapy.

Methods and Results

Artonin I, a flavonoid obtained from Morus mesozygia Stapf., inhibited the bacterial efflux pump and induced depolarization of the cell membrane. To study the dose-dependent production of reactive oxygen species in MDR cells by artonin I, lucigenin chemiluminescence assay was employed. Reversal of multidrug resistance by artonin I, in combination with antibiotics, was measured by a fractional inhibitory concentration index assay. The effect of artonin I on ultrastructural features was studied by microscopy. Artonin I increased the penetration of ethidium bromide by blocking the efflux mechanism. It also helped anionic probe DiBAC4 (3) to bind with the lipid-rich cellular components by causing depolarization of the cell membrane. Artonin I reversed multidrug resistance and increased the susceptibility of existing antibiotics by lowering their minimum inhibitory concentrations (MICs).

Conclusions

Artonin I was identified both as a new antibacterial agent and a helper molecule to potentiate the action of otherwise inactive antibiotics.

Significance and Impact of the Study

Artonin I can be developed as potential antimicrobial and resistance reversal agent.