Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA.
J Med Microbiol. 2013 Jan;62(Pt 1):69-77. doi: 10.1099/jmm.0.047811-0. Epub 2012 Sep 27.
There is a clear clinical need for alternative types of non-antibiotic biocides due to the rising global health concern of microbial drug resistance. In this work, a novel antibacterial concept was delineated that utilized hyperosmotic stress (H) in concert with membrane-disrupting nanoemulsions (NEs). The antibacterial effects of either H or a NE, as well as in combination (H+NE), were assessed in vitro using an Escherichia coli model. It was found that exposure to H or NE alone produced dose-dependent bacteriostatic and bactericidal effects, respectively. However, the bactericidal action of NE was significantly amplified in the presence of H. Outcomes following H+NE exposure included rapid efflux of K(+) and nucleic acids, increased membrane permeability and a reduction in both intracellular ATP and cell viability. Further inspection of morphology by electron microscopy highlighted cell shrinkage, membrane dissolution and bacteriolysis. Pathogen inactivation occurred immediately upon contact with H+NE. The effects of H, NE and H+NE against Enterococcus faecalis, Staphylococcus aureus and meticillin-resistant S. aureus isolates were also examined. Similar to the Escherichia coli model, H+NE showed antibacterial synergism in these organisms when classified by the Chou-Talalay combination index for two-agent interactions. This synergistic interaction suggests that the H+NE platform may potentially serve as a new paradigm in disinfectants, antiseptics and antibacterial wound dressings. The H+NE mechanism of action was termed osmopermeation, as a descriptor for the underlying inactivation process.
由于全球对微生物药物耐药性的担忧日益加剧，人们对替代抗生素类生物杀灭剂的需求日益迫切。在这项工作中，提出了一种利用高渗透压（H）与膜破坏纳米乳液（NE）协同作用的新型抗菌概念。利用大肠杆菌模型，在体外评估了 H 或 NE 单独作用以及联合作用（H+NE）的抗菌效果。结果发现，单独暴露于 H 或 NE 会分别产生剂量依赖性的抑菌和杀菌作用。然而，在 H 的存在下，NE 的杀菌作用显著增强。H+NE 暴露后的结果包括 K(+)和核酸的快速外排、膜通透性增加以及细胞内 ATP 和细胞活力的降低。电子显微镜进一步观察形态学变化，突出显示细胞收缩、膜溶解和细菌溶解。病原体在与 H+NE 接触时立即失活。还研究了 H、NE 和 H+NE 对粪肠球菌、金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌分离株的作用。与大肠杆菌模型类似，当根据两药相互作用的 Chou-Talalay 组合指数对这些生物体进行分类时，H+NE 显示出协同抗菌作用。这种协同相互作用表明，H+NE 平台可能有望成为消毒剂、防腐剂和抗菌伤口敷料的新范例。H+NE 的作用机制被称为渗透压渗透，作为潜在失活动力学的描述符。
