Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong 519041, China.
J Proteomics. 2020 Mar 20;215:103666. doi: 10.1016/j.jprot.2020.103666. Epub 2020 Jan 23.
Berberine is an isoquinoline alkaloid found in many plants. Although berberine is known to possess the antibacterial activity against Streptococcus pyogenes, the mechanism underlying it is not fully understood. In the current study, to investigate the molecular mechanism how berberine exerts its antibacterial effects, quantitative proteomics was conducted to investigate differential expressed proteins in S. pyogenes in response to berberine treatment. KEGG pathways analysis revealed that berberine regulated proteins were mainly involved in carbohydrate metabolism, fatty acid biosynthesis, pyrimidine metabolism, RNA degradation, ribosome, purine metabolism, DNA replication and repair and oxidative phosphorylation pathways. Moreover, we found that berberine induced the accumulation of reactive oxygen species (ROS), whereas inhibition of ROS generation with antioxidant N-acetyl L-cysteine could block the berberine induced antibacterial effects. Collectively, we demonstrated that berberine exerts its antibacterial effects by perturbing carbohydrate metabolism, which therefore generate ROS to damage the DNA, protein and lipids biosynthesis, ultimately trigger cell lethality. These findings provide novel insights into the mechanism of berberine as an antimicrobial drug to control diseases caused by S. pyogenes. SIGNIFICANCE: Streptococcus pyogenes is the major cause of invasive bacterial disease in human, which leads to hundreds of million cases annually and over 500,000 deaths due to severe infections. Berberine is an isoquinoline alkaloid from medicinal plants, which possesses a variety of pharmacological effects including antibacterial. In this work, proteomic analysis revealed that berberine affected carbohydrate metabolism, DNA, protein and fatty acid biosynthesis and oxidative phosphorylation pathways in S. pyogenes. And further experimental results showed that berberine exerts its antibacterial effects against Streptococcus pyogenes by stimulated the generation of reactive oxygen species (ROS). These data provide novel insights into the effect of berberine on oxidative stress as an antimicrobial drug.
小檗碱是一种存在于许多植物中的异喹啉生物碱。虽然小檗碱已知具有抗酿脓链球菌的抗菌活性，但它的作用机制尚未完全了解。在本研究中，为了研究小檗碱发挥其抗菌作用的分子机制，采用定量蛋白质组学方法研究了小檗碱处理后酿脓链球菌中差异表达的蛋白质。KEGG 途径分析显示，小檗碱调节的蛋白质主要参与碳水化合物代谢、脂肪酸生物合成、嘧啶代谢、RNA 降解、核糖体、嘌呤代谢、DNA 复制和修复以及氧化磷酸化途径。此外，我们发现小檗碱诱导活性氧（ROS）的积累，而抗氧化剂 N-乙酰-L-半胱氨酸抑制 ROS 的产生可以阻断小檗碱诱导的抗菌作用。总之，我们证明小檗碱通过扰乱碳水化合物代谢发挥其抗菌作用，从而产生 ROS 来破坏 DNA、蛋白质和脂质生物合成，最终引发细胞死亡。这些发现为小檗碱作为一种控制酿脓链球菌引起的疾病的抗菌药物的作用机制提供了新的见解。
酿脓链球菌是人类侵袭性细菌病的主要原因，每年导致数亿例病例，并因严重感染导致超过 50 万人死亡。小檗碱是一种来源于药用植物的异喹啉生物碱，具有多种药理作用，包括抗菌作用。在这项工作中，蛋白质组学分析表明，小檗碱影响酿脓链球菌的碳水化合物代谢、DNA、蛋白质和脂肪酸生物合成以及氧化磷酸化途径。进一步的实验结果表明，小檗碱通过刺激活性氧（ROS）的产生发挥其对酿脓链球菌的抗菌作用。这些数据为小檗碱作为一种抗菌药物通过氧化应激发挥作用提供了新的见解。
