Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections

Abstract

Berberine is an isoquinoline alkaloid widely used in the treatment of microbial infections. Recent studies have shown that berberine can enhance the inhibitory efficacy of antibiotics against clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA). However, the underlying mechanisms are poorly understood. Here, we demonstrated that sub-minimum inhibitory concentrations (MICs) of berberine exhibited no bactericidal activity against MRSA, but affected MRSA biofilm development in a dose dependent manner within the concentration ranging from 1 to 64 μg/mL. Further study indicated that berberine inhibited MRSA amyloid fibrils formation, which consist of phenol-soluble modulins (PSMs). Molecular dynamics simulation revealed that berberine could bind with the phenyl ring of Phe19 in PSMα2 through hydrophobic interaction. Collectively, berberine can inhibit MRSA biofilm formation via affecting PSMs’ aggregation into amyloid fibrils, and thereby enhance bactericidal activity of antibiotics. These findings will provide new insights into the multiple pharmacological properties of berberine in the treatment of microbial-generated amyloid involved diseases.

Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids)

“…This compound altered bacterial DNA synthesis. It also hinders the biofilm formation of methicillin-resistant S. aureus (MRSA) in a concentration-dependent manner ranging from 1 to 64 μg/mL via inhibiting phenolsoluble modulins (PSMs) aggregation into amyloid fibrils (Chu et al, 2016).…”

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

“…BBR is one of the commonly used drugs in the treatment of intestinal infections in China [6]. In addition to its broad spectrum bacteriostatic effects [7][8][9], BBR is reported to have anti-inflammatory, anti-oxidant, anti-tumor, hypoglycemic and anti-cardiac arrhythmia qualities [10][11][12][13][14]. Studies also reported that BBR had good bacteriostatic effect on E. coli and Bacillus subtilis [15].…”

“…Subsequent studies reported that the MIC of BBR against the MRSA reference strain ATCC33591 was 128 µg/mL. BBR can affect the aggregation of amyloid fibers in PSMs of MRSA biofilm, thus inhibiting the formation of MRSA biofilm and increasing the bactericidal activity of antibiotics [9]. Recent studies have reported that BBR had bacteriostatic effects on MRSA, yet no specific study on its bacteriostatic mechanism has been reported.…”

“…The MIC of BBR on reference strain USA300 is 128 ug/mL, while the MIC of BBR on 26 clinical isolated MRSA strains is 32-256 ug/mL, indicating that BBR has strong bacteriostatic effect both on USA300 and clinical isolated strains, which is consistent with the previous research results of Chu, M. etc. [9], who reported that the MIC of BBR on reference strain ATCC33591 was 128 ug/mL ( Table 2).…”

The Combined Antibacterial Effects of Sodium New Houttuyfonate and Berberine Chloride against Growing and Persistent Methicillin-Resistant and Vancomycin-Intermediate Staphylococcus aureus

“…Cortex and Coptis chinensis Franch and fully chemically synthesized now [14], has been widely used to treat bacterial diarrhea and gastroenteritis for many years in China [15,16]. Several studies have demonstrated the antibacterial activities of berberine alone or as a synergist of antibiotics [17][18][19][20][21][22].…”