title: Synergistic bactericidal activity between hyperosmotic stress and membrane-disrupting nanoemulsions.
abstract: 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.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Connell
authors.affiliation: Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA.|Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Riyi
authors.initials: R
authors.lastname: Shi
mesh_terms: D001419:Bacteria / Q000648:ultrastructure*; D002462:Cell Membrane; D002463:Cell Membrane Permeability; D003600:Cytosol; D050296:Microbial Viability; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures; D009997:Osmotic Pressure; D011188:Potassium / Q000737:chemistry
chemical_list: D011188:Potassium