EVALUATION OF MECA AND YYCFG GENE EXPRESSION DYNAMICS IN METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) UNDER THE INFLUENCE OF PHENOLIC COMPOUNDS, BORNEOL AND EXTRACT OF SALVIA STEPPE (SALVIA STEPPOSA DES.-SHOST)

Introduction. Staphylococcus aureus demonstrates sufficient adaptive potential under external stress conditions, which may determine its key role in the etiology of hospital-acquired infections. The observed exponential growth of strains with multiple antibiotic resistance over the past decades indicates that adaptation mechanisms contribute to the survival and spread of S. aureus under conditions of intensive hospital exposure to antimicrobial agents. This phenomenon significantly complicates the clinical treatment of infections and poses a serious threat to the healthcare system. Despite the active study of changes in the activity of genes associated with antibiotic resistance under various stress conditions, the role of phenolic compounds in the regulation of gene expression in MRSA has been insufficiently studied. In particular, there are practically no data on the effect of phenolic compounds and borneol on the expression of the MecA and YycFG genes, which determines the relevance of this work.

Aim. To evaluate the dynamics of MecA and YycFG gene expression in methicillin-resistant Staphylococcus aureus (MRSA) under the influence of phenolic compounds (rosmarinic, chlorogenic and ferulic acids), borneol and Salvia Stepposa Des. -Shost leaf extract.

Materials and methods. The MICs of the studied compounds were determined using the serial dilution micromethod. To evaluate the effect of the studied compounds, daily MRSA cultures were additionally incubated with the studied compounds at subinhibitory concentrations (1/2 MIC) for 4 hours. Changes in MecA and YycFG expression were analyzed by quantitative PCR (ΔΔCt, log2 Fold Change). GyrB expression was assessed as an endogenous control. Statistical processing included the Kruskal-Wallis, Wilcoxon and Mann-Whitney tests (p=0.05).

Results and discussion. The results showed that phenolic compounds, borneol and Salvia stepposa leaf extract reduced MecA expression by 2.17-5 times (p=0.043) and increased YycFG by 1.84-2.45 times (p=0.043). Rosmarinic and chlorogenic acids showed the greatest activity towards MecA.

Conclusion. Chlorogenic and rosmarinic acids have significant potential to suppress MecA expression in MRSA. Rosmarinic acid reduces MecA expression by 5 times, chlorogenic acid by 4 times. These results allow us to consider the studied compounds as promising candidates for the development of new antimicrobial drugs or adjuvants that enhance the effect of antibiotics. In the future, the synergistic combination of rosmarinic and chlorogenic acids with β-lactams may become an effective tool for overcoming MRSA resistance.

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