Artonin I inhibits multidrug resistance in Staphylococcus aureus and potentiates the action of inactive antibiotics in vitro
Article first published online: 5 AUG 2014
© 2014 The Society for Applied Microbiology
Journal of Applied Microbiology
Volume 117, Issue 4, pages 996–1011, October 2014
How to Cite
Farooq, S., Wahab, A.-T.-., Fozing, C.D.A., Rahman, A.-U.-. and Choudhary, M. I. (2014), Artonin I inhibits multidrug resistance in Staphylococcus aureus and potentiates the action of inactive antibiotics in vitro. Journal of Applied Microbiology, 117: 996–1011. doi: 10.1111/jam.12595
- Issue published online: 15 SEP 2014
- Article first published online: 5 AUG 2014
- Accepted manuscript online: 4 JUL 2014 06:35AM EST
- Manuscript Accepted: 27 JUN 2014
- Manuscript Revised: 26 JUN 2014
- Manuscript Received: 24 FEB 2014
- Pakistan Academy of Sciences (PAS). Grant Number: 5-9/PAS/1562
- artonin I;
- cell membrane depolarization;
- combination therapy;
- efflux pump inhibitor;
- Morus mesozygiya Stapf.;
- multidrug-resistant Staphylococcus aureus;
- reactive oxygen species;
- reversal of multidrug resistance
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).
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.