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

2016; Nature Portfolio; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/srep24748

2045-2322

Ming Chu, Mingbo Zhang, Yanchen Liu, Jiarui Kang, Zheng-yun Chu, Kailin Yin, Lingyu Ding, Ran Ding, Rong-xin Xiao, Yi-nan Yin, Xiaoyan Liu, Yuedan Wang,

Alkaloids: synthesis and pharmacology

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.