Budeyri Gokgoz Nilay, Avci Fatma Gizem, Yoneten Kubra Karaosmanoglu, Alaybeyoglu Begum, Ozkirimli Elif, Sayar Nihat Alpagu, Kazan Dilek, Sariyar Akbulut Berna
1 Department of Bioengineering, Marmara University , Istanbul, Turkey .
2 Department of Chemical Engineering, Bogazici University , Istanbul, Turkey .
Microb Drug Resist. 2017 Jul;23(5):531-544. doi: 10.1089/mdr.2016.0063. Epub 2016 Nov 17.
Berberine is a plant-derived alkaloid possessing antimicrobial activity; unfortunately, its efflux through multidrug resistance pumps reduces its efficacy. Cellular life span of Escherichia coli is generally shorter with prolonged berberine exposure; nevertheless, about 30% of the cells still remain robust following this treatment. To elucidate its mechanism of action and to identify proteins that could be involved in development of antimicrobial resistance, protein profiles of E. coli cells treated with berberine for 4.5 and 8 hours were compared with control cells. A total of 42 proteins were differentially expressed in cells treated with berberine for 8 hours when compared to control cells. In both 4.5 and 8 hours of berberine-treated cells, carbohydrate and peptide uptake regimens remained unchanged, although amino acid maintenance regimen switched from transport to synthesis. Defect in cell division persisted and this condition was confirmed by images obtained from scanning electron microscopy. Universal stress proteins were not involved in stress response. The significant increase in the abundance of elongation factors could suggest the involvement of these proteins in protection by exhibiting chaperone activities. Furthermore, the involvement of the outer membrane protein OmpW could receive special attention as a protein involved in response to antimicrobial agents, since the expression of only this porin protein was upregulated after 8 hours of exposure.
黄连素是一种具有抗菌活性的植物源生物碱；不幸的是，其通过多药耐药泵的外排作用降低了其疗效。随着黄连素暴露时间延长，大肠杆菌的细胞寿命通常会缩短；然而，约30%的细胞在这种处理后仍保持活力。为阐明其作用机制并鉴定可能参与抗菌耐药性发展的蛋白质，将用黄连素处理4.5小时和8小时的大肠杆菌细胞的蛋白质谱与对照细胞进行了比较。与对照细胞相比，用黄连素处理8小时的细胞中共有42种蛋白质差异表达。在黄连素处理4.5小时和8小时的细胞中，碳水化合物和肽的摄取方式均未改变，尽管氨基酸维持方式从转运转变为合成。细胞分裂缺陷持续存在，扫描电子显微镜图像证实了这种情况。普遍应激蛋白不参与应激反应。延伸因子丰度的显著增加可能表明这些蛋白质通过表现出伴侣活性参与保护作用。此外，外膜蛋白OmpW作为一种参与对抗菌剂反应的蛋白质可能会受到特别关注，因为仅这种孔蛋白在暴露8小时后表达上调。
