Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections.
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.
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Key Laboratory of Medical Immunology, Ministry of Health, Beijing, 100191, China.
Ming
M
Chu
Pharmacy Departments, Liao Ning University of Traditional Chinese Medicine, Liao Ning, 116600, China.
Ming-Bo
MB
Zhang
Pharmacy Departments, Liao Ning University of Traditional Chinese Medicine, Liao Ning, 116600, China.
Yan-Chen
YC
Liu
Department of Pathology, the First Affiliated Hospital of General Hospital of Chinese People's Liberation Army, Beijing, 100048, China.
Jia-Rui
JR
Kang
Pharmacy Departments, Liao Ning University of Traditional Chinese Medicine, Liao Ning, 116600, China.
Zheng-Yun
ZY
Chu
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Key Laboratory of Medical Immunology, Ministry of Health, Beijing, 100191, China.
Kai-Lin
KL
Yin
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Key Laboratory of Medical Immunology, Ministry of Health, Beijing, 100191, China.
Ling-Yu
LY
Ding
Pharmacy Departments, Liao Ning University of Traditional Chinese Medicine, Liao Ning, 116600, China.
Ran
R
Ding
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Rong-Xin
RX
Xiao
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Yi-Nan
YN
Yin
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Xiao-Yan
XY
Liu
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.|Key Laboratory of Medical Immunology, Ministry of Health, Beijing, 100191, China.
Yue-Dan
YD
Wang
D000682:Amyloid / Q000037:antagonists & inhibitors; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D055503:Protein Multimerization
D000682:Amyloid; D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; C025971:staphylococcal delta toxin; D001599:Berberine