title: Antibacterial synergy between rosmarinic acid and antibiotics against methicillin-resistantStaphylococcus aureus.
abstract: OBJECTIVE
  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-resistantStaphylococcus aureus(MRSA) which is resistant to all kinds of β-lactams, threatens even most potent antibiotics. To improve the efficiency of antibiotics against multi-drug resistant bacteria and to reduce the antibiotic dose, the antibacterial activity and the synergistic effect of RA with standard antibiotics againstS. aureusand MRSA was investigated.
  
  
  METHODS
  Antibacterial activity of RA againstS. aureusand a 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 againstS. aureusand MRSA was studied by broth checkerboard method and time-kill kinetic assay. Effect of RA on microbial surface components recognizing adhesive matrix molecules (MSCRAMM's) ofS. aureusand MRSA was studied using sodium dodecyl sulfate - polyacrylamide gel electrophoresis.
  
  
  RESULTS
  MIC of RA was found to be 0.8 and 10 mg/ml againstS. aureusand MRSA, respectively. RA was synergistic with vancomycin, ofloxacin, and amoxicillin againstS. aureusand only with vancomycin against MRSA. The time-kill analysis revealed that synergistic combinations were a more effective than individual antibiotics. MSCRAMM's protein expression ofS. aureusand MRSA was markedly suppressed by RA + vancomycin combination rather than RA alone.
  
  
  CONCLUSIONS
  The synergistic effects of RA with antibiotics were observed againstS. aureusand MRSA. RA showed inhibitory effect on the surface proteins MSCRAMM's. Even though RA was shown to exhibit a 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.
authors.affiliation: Department of Pharmaceutical Technology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, Tamil Nadu, India.
authors.forename: Sanmuga Priya
authors.initials: SP
authors.lastname: Ekambaram
authors.affiliation: Department of Pharmaceutical Technology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, Tamil Nadu, India.
authors.forename: Senthamil Selvan
authors.initials: SS
authors.lastname: Perumal
authors.affiliation: Department of Pharmaceutical Technology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, Tamil Nadu, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: Department of Pharmaceutical Technology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, Tamil Nadu, India.
authors.forename: Nathiya
authors.initials: N
authors.lastname: Marappan
authors.affiliation: Department of Pharmaceutical Technology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, Tamil Nadu, India.
authors.forename: Sabari Srinivasan
authors.initials: SS
authors.lastname: Gajendran
authors.affiliation: Department of Pharmaceutical Technology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, Tamil Nadu, India.
authors.forename: Vinodhini
authors.initials: V
authors.lastname: Viswanathan
keywords: Antimicrobial resistance; methicillin-resistant Staphylococcus aureus; microbial surface components recognizing adhesive matrix molecules; rosmarinic acid; synergy