Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, USA.
Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Biosens Bioelectron. 2022 May 15;204:114045. doi: 10.1016/j.bios.2022.114045. Epub 2022 Jan 29.
Antibiotic resistance is a growing global health concern due to the decreasing number of antibiotics available for therapeutic use as more drug-resistant bacteria develop. Changes in the membrane properties of Gram-negative bacteria can influence their response to antibiotics and give rise to resistance. Thus, understanding the interactions between the bacterial membrane and antibiotics is important for elucidating microbial membrane properties to use for designing novel antimicrobial drugs. To study bacterial membrane-antibiotic interactions, we created a surface-supported planar bacterial outer membrane model on an optically-transparent, conducting polymer surface (poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)). This model enables membrane characterization using fluorescence microscopy and electrochemical impedance spectroscopy (EIS). The membrane platform is fabricated using outer membrane vesicles (OMVs) isolated from clinically relevant Gram-negative bacteria, enterohemorrhagic Escherichia coli. This approach enables us to mimic the native components of the bacterial membrane by incorporating native lipids, membrane proteins, and lipopolysaccharides. Using EIS, we determined membrane impedance and captured membrane-antibiotic interactions using the antibiotics polymyxin B, bacitracin, and meropenem. This sensor platform incorporates aspects of the biological complexity found in bacterial outer membranes and, by doing so, offers a powerful, biomimetic approach to the study of antimicrobial drug interactions.
由于可供治疗用途的抗生素数量不断减少,而更多具有耐药性的细菌不断出现,抗生素耐药性成为一个日益严重的全球健康问题。革兰氏阴性菌细胞膜特性的变化会影响其对抗生素的反应,从而导致耐药性的产生。因此,了解细菌细胞膜与抗生素之间的相互作用对于阐明微生物细胞膜特性,从而设计新型抗菌药物非常重要。为了研究细菌细胞膜-抗生素相互作用,我们在光学透明导电聚合物表面(聚(3,4-亚乙基二氧噻吩)聚苯乙烯磺酸盐(PEDOT:PSS))上创建了一个表面支撑的平面细菌外膜模型。该模型能够使用荧光显微镜和电化学阻抗谱(EIS)对膜进行特性分析。该膜平台是使用从临床相关革兰氏阴性菌,肠出血性大肠杆菌中分离出的外膜囊泡(OMVs)来制造的。这种方法能够通过整合天然脂质、膜蛋白和脂多糖来模拟细菌膜的天然成分。我们使用 EIS 确定了膜阻抗,并使用抗生素多粘菌素 B、杆菌肽和美罗培南捕获了膜-抗生素相互作用。该传感器平台整合了细菌外膜中发现的生物复杂性的各个方面,通过这种方式,为研究抗菌药物相互作用提供了一种强大的仿生方法。