School of Science, RK University, Rajkot, Gujarat, India.
Department of Biotechnology, College of Agriculture, Junagadh Agricultural University, Junagadh, Gujarat, India.
Life Sci. 2019 Aug 1;230:178-187. doi: 10.1016/j.lfs.2019.05.072. Epub 2019 May 29.
With the purpose of exploring combinatorial options that could enhance the bactericide efficacy of linezolid against Gram-negative bacteria, we assessed the extent of combination of nano-silver and linezolid.
In this study, we selected Escherichia coli MTCC 443 as a model to study the combinatorial effect of nano-silver and linezolid to combat efflux-mediated resistance in Gram-negative bacteria. The acting mechanism of nano-silver on E. coli MTCC 443 was investigated by evaluating interaction of nano-silver with bacterial membrane as well as bacterial surface charge, morphology, intracellular leakages and biological activities of membrane bound respiratory chain dehydrogenase and deoxyribonucleic acids (DNA) of the cells following treatment with nano-silver.
The alternation of zeta potential due to the interaction of nano-silver towards bacterial membrane proteins was correlated with enhancement of membrane permeability, which allows the penetration of linezolid into the cells. In addition, the binding affinity of nano-silver towards bacterial membrane depressed biological activities of membrane bound respiratory chain dehydrogenases and DNA integrity.
Our findings suggested that nano-silver could not only obstruct the activities of efflux pumps, but also altered membrane integrity at the same time and thus increased the cytoplasmic concentration of the linezolid to the effective level.
为了探索能够增强利奈唑胺对革兰氏阴性菌杀菌效果的组合方案,我们评估了纳米银与利奈唑胺联合使用的程度。
在这项研究中,我们选择大肠杆菌 MTCC 443 作为模型,研究纳米银和利奈唑胺联合使用对抗革兰氏阴性菌外排泵介导耐药性的组合效应。通过评估纳米银与细菌膜以及细菌表面电荷的相互作用、纳米银处理后细胞的形态、细胞内渗漏以及膜结合呼吸链脱氢酶和脱氧核糖核酸(DNA)的生物活性,研究了纳米银对大肠杆菌 MTCC 443 的作用机制。
由于纳米银与细菌膜蛋白的相互作用而导致的zeta 电位改变与膜通透性的增强相关,这使得利奈唑胺能够进入细胞。此外,纳米银与细菌膜的结合亲和力抑制了膜结合呼吸链脱氢酶的生物活性和 DNA 的完整性。
我们的研究结果表明,纳米银不仅可以阻止外排泵的活性,还可以同时改变膜的完整性,从而将利奈唑胺的细胞质浓度提高到有效水平。