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Proteomic investigation into the action mechanism of berberine against Streptococcus pyogenes.
Journal of Proteomics ( IF 3.3 ) Pub Date : 2020-01-23 , DOI: 10.1016/j.jprot.2020.103666
Gao-Fei Du 1 , Yao-Jin Le 2 , Xuesong Sun 1 , Xiao-Yan Yang 3 , Qing-Yu He 1
Affiliation  

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.



中文翻译:

蛋白质组学研究小Str碱对化脓性链球菌的作用机理。

小ber碱是许多植物中发现的异喹啉生物碱。尽管已知小ber碱对化脓性链球菌具有抗菌活性,但其基础机理尚不完全清楚。在当前的研究中,为了研究小碱如何发挥其抗菌作用的分子机制,进行了定量蛋白质组学研究化脓性链球菌中的差异表达蛋白对小ber碱治疗有反应。KEGG通路分析表明,小ber碱调节蛋白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,我们发现黄连素诱导活性氧(ROS)的积累,而抗氧化剂N抑制ROS的生成-乙酰基L-半胱氨酸可以阻断小ber碱诱导的抗菌作用。总的来说,我们证明了小碱通过干扰碳水化合物的代谢发挥其抗菌作用,因此会产生ROS来破坏DNA,蛋白质和脂质的生物合成,最终引发细胞致死性。这些发现为黄连素作为控制化脓性链球菌引起的疾病的抗菌药物的机理提供了新颖的见解。

意义

化脓性链球菌是人类侵袭性细菌疾病的主要原因,每年导致亿万病例,由于严重感染导致超过500,000例死亡。小ber碱是一种来自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,蛋白质组学分析显示,小ber碱影响化脓性链球菌中的碳水化合物代谢,DNA,蛋白质和脂肪酸的生物合成以及氧化磷酸化途径。进一步的实验结果表明,小ber碱对化脓性链球菌具有抗菌作用。通过刺激活性氧(ROS)的产生。这些数据为小novel碱作为抗微生物药对氧化应激的作用提供了新颖的见解。

更新日期:2020-01-23
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