Effect of Ruta graveolens Extract on the Major Virulence Factors in Methicillin Resistant Staphylococcus aureus

Abstract

Purpose: Rising Antibiotic Resistance has put the world in real threat. Methicillin resistant Staphylococcus aureus (MRSA), is a predominant cause of suppurative chronic skin and soft-tissue infections. Novel insights have focused the light on plant extracts. In this study, Ruta graveolens ethanolic active extract was tested for its potential anti-virulence activities in MRSA. Materials and Methods: A total of 100 MRSA strains causing skin and soft tissue infections were isolated and antibiotic susceptibility testing was done. Ability to form biofilm was tested phenotypically. Furthermore, the antimicrobial activity of Ruta graveolens was evaluated followed by detection of its Minimum inhibitory concentration (MIC). The inhibitory activity of this extract on biofilm formation was investigated. Afterwards, we investigated its effect on the transcription of biofilm-related genes and mecA gene. Results: All tested isolates were sensitive to Vancomycin and Linezolid while high resistance was noted with both Fusidic acid (83%) and Gentamicin (68%). (83%) of the isolates were biofilm producers. Ruta graveolens extract showed strong antimicrobial activity against the MRSA strains with MIC 0.78 mg/mL. At subinhibitory concentration (1/2 MIC), the extract had high biofilm inhibitory effects with mean inhibition (70%). Moreover, transcriptional analysis results showed that the mean percentages of inhibition in expression of mecA, icaA and icaD genes were 52.3%, 34.8% and 33.7%, respectively, in which all showed statistically significant difference (p ≤ 0.05). Conclusion: The current study proposes the ability of Ruta graveolens extract to reduce the biofilm formation and antibiotic resistance of MRSA through downregulation of some biofilm forming genes and mecA gene which confers resistance to B-lactam antibiotics. This may decrease our reliance on antibiotics and improve our ability to effectively treat biofilm-related skin and soft-tissue infections caused by MRSA.