The bacteriostatic effect and mechanism of berberine on Methicillin resistant Staphylococcus aureus in vitro

Abstract

Background: To observe the bacteriostatic effect of berberine on MRSA, while also exploring the bacteriostatic mechanism of BBR on MRSA. Methods: The MIC of BBR, gentamicin, levofloxacin，amikacin was determined by broth microdilution, while the MICs of BBR combined with gentamicin, levofloxacin，amikacin against MRSA were determined using microdilution checkerboard. Time-killing test were used to determine the kinetics of BBR combined with antibiotics for MRSA. We used conductivity to assess the changes in membrane permeability in response to BBR on MRSA, while also investigating the changes in MRSA morphology by TEM. RNA-sequencing was used to analyze the expression of differentially expressed genes in USA300 after its treatment with BBR. Results: The MICs range of BBR on MRSA was 32-256 µg/mL. The range of FICIs of BBR combined with gentamicin, levofloxacin，amikacin were 0.53-1.06, 0.62-1.5, 0.16-1.25. After co-culturing MRSA with BBR at 512 ug/mL, 64 ug/mL,8 ug/mL, respectively, the conductivity of these group increased by 8.14%,13.08% and 12.01%, respectively. Using TEM, we found that low-concentration of BBR had no significant effect on MRSA structure, medium-concentration of BBR thinned the cell wall of MRSA, while high-concentration of BBR destroyed cell wall, leading to bacterial lysis. RNA-sequencing results showed that there were 754 differentially expressed genes in the high-concentration group compared with the control group, of which 561 genes were up-regulated and 193 genes were down-regulated. Compared with the low-concentration group, there were 590 differentially expressed genes, of which 402 genes were up-regulated and 188 genes were down-regulated. Compared with the control group, 19 genes were differentially expressed in the low-concentration group, of which 11 genes were up-regulated,8 genes were down-regulated. Conclusions: BBR displayed an excellent bacteriostatic effect on MRSA. BBR combined with antibiotics significantly enhanced the bacteriostatic effect on MRSA. BBR inhibited bacteria by destroying the structure of cell wall. RNA-sequencing results demonstrated that the expression of cell wall hydrolysis genes and virulence factor were significantly differentially expressed on MRSA.

Tackling strong biofilm and multi-virulent vancomycin-resistant Staphylococcus aureus via natural alkaloid-based porous nanoparticles: perspective towards near future eradication

“…Similarly, MRSA adhesion and intracellular invasion were notably decreased post treatment with berberine (Yu et al, 2005). Moreover, expression of MRSA cell wall hydrolysis, serine protease (Wang et al, 2020), and biofilm (Zhang et al, 2022)-associated genes were significantly repressed following treatment with berberine. A previous study demonstrated that higher doses of berberine were more effective in increasing cell membrane permeability of MRSA (Xia et al, 2022).…”

Research progress of ellagic acid in systemic and oral diseases

“…The content of MDA can reflect the degree of lipid peroxidation in the body or organs. Yonar et [10] al. took rainbow trout as the research object and tested the antioxidant activity of ellagic acid at 50, 100 and 150 mg/kg mb respectively.…”