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Antibacterial synergy between Rosmarinic acid and antibiotics against Methicillin resistant Staphylococcus aureus

Sanmuga Priya Ekambaram, Senthamil Selvan Perumal, Ajay Balakrishnan, Nathiya Marappan, Sabari Srinivasan Gajendran, Vinodhini Viswanathan.


Aim/Background: Medicinal plants have ability to resist microorganisms by synthesizing secondary metabolites such as phenols. Rosmarinic acid (RA) is a phenylpropanoid widely distributed in plants and well known as therapeutic and cosmetic agent. Methicillin-resistant Staphylococcus aureus (MRSA) which is resistant to all kinds of β-lactams, threatens even most potent antibiotics. To improve efficiency of antibiotics against multi-drug resistant bacteria and to reduce the antibiotic dose, the antibacterial activity and the synergistic effect of rosmarinic acid with standard antibiotics against Staphylococcus aureus (S. aureus) and MRSA was investigated.
Materials and Methods: Antibacterial activity of RA against S. aureus and clinical isolate of MRSA was evaluated by agar well diffusion method. Minimum inhibitory concentration (MIC) of RA was determined by broth dilution method. Synergism of RA with various antibiotics against S. aureus and MRSA was studied by broth checker board method and time kill kinetic assay. Effect of RA on MSCRAMM’s (Microbial Surface Components Recognising Adhesive Matrix Molecules) of S. aureus and MRSA was studied using sodium dodecyl sulphate - polyacrylamide gel electrophoresis (SDS-PAGE).
Results: MIC of RA was found to be 0.8 mg/ml and 10 mg/ml against S. aureus and MRSA respectively. RA was synergistic with vancomycin, ofloxacin and amoxicillin against S. aureus and only with vancomycin against MRSA. The time kill analysis revealed that synergistic combinations were more effective than individual antibiotics. MSCRAMM’s protein expression of S. aureus and MRSA was markedly suppressed by RA + vancomycin combination rather than RA alone.
Conclusion: The synergistic effects of RA with antibiotics were observed against S. aureus and MRSA. RA showed inhibitory effect on the surface proteins MSCRAMM’s. Even though RA was shown to exhibit synergistic effect with antibiotics, the MIC was found to be higher. Thus further studies on increasing the efficacy of RA can develop it as an adjuvant for antibiotics.

Key words: Rosmarinic acid, MRSA, synergy, antimicrobial resistance, MSCRAMM’s.

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