title: Nanotransformation of Vancomycin Overcomes the Intrinsic Resistance of Gram-Negative Bacteria.
abstract: The increased emergence of antibiotic-resistant bacteria is a growing public health concern, and although new drugs are constantly being sought, the pace of development is slow compared with the evolution and spread of multidrug-resistant species. In this study, we developed a novel broad-spectrum antimicrobial agent by simply transforming vancomycin into nanoform using sonochemistry. Vancomycin is a glycopeptide antibiotic largely used for the treatment of infections caused by Gram-positive bacteria but inefficient against Gram-negative species. The nanospherization extended its effect toward Gram-negative Escherichia coli and Pseudomonas aeruginosa, making these bacteria up to 10 and 100 times more sensitive to the antibiotic, respectively. The spheres were able to disrupt the outer membranes of these bacteria, overcoming their intrinsic resistance toward glycopeptides. The penetration of nanospheres into a Langmuir monolayer of bacterial membrane phospholipids confirmed the interaction of the nanoantibiotic with the membrane of E. coli cells, affecting their physical integrity, as further visualized by scanning electron microscopy. Such mechanism of antibacterial action is unlikely to induce mutations in the evolutionary conserved bacterial membrane, therefore reducing the possibility of acquiring resistance. Our results indicated that the nanotransformation of vancomycin could overcome the inherent resistance of Gram-negative bacteria toward this antibiotic and disrupt mature biofilms at antibacterial-effective concentrations.
authors.affiliation: Grup de Biotecnologia Molecular i Industrial, Department of Chemical Engineering, Universitat Politècnica de Catalunya , Rambla Sant Nebridi 22, Terrassa 08222, Spain.
authors.forename: Margarida M
authors.initials: MM
authors.lastname: Fernandes
authors.affiliation: Grup de Biotecnologia Molecular i Industrial, Department of Chemical Engineering, Universitat Politècnica de Catalunya , Rambla Sant Nebridi 22, Terrassa 08222, Spain.
authors.forename: Kristina
authors.initials: K
authors.lastname: Ivanova
authors.affiliation: Grup de Biotecnologia Molecular i Industrial, Department of Chemical Engineering, Universitat Politècnica de Catalunya , Rambla Sant Nebridi 22, Terrassa 08222, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Hoyo
authors.affiliation: Grup de Biotecnologia Molecular i Industrial, Department of Chemical Engineering, Universitat Politècnica de Catalunya , Rambla Sant Nebridi 22, Terrassa 08222, Spain.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Pérez-Rafael
authors.affiliation: Grup de Biotecnologia Molecular i Industrial, Department of Chemical Engineering, Universitat Politècnica de Catalunya , Rambla Sant Nebridi 22, Terrassa 08222, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Francesko
authors.affiliation: Grup de Biotecnologia Molecular i Industrial, Department of Chemical Engineering, Universitat Politècnica de Catalunya , Rambla Sant Nebridi 22, Terrassa 08222, Spain.
authors.forename: Tzanko
authors.identifier: http://orcid.org/0000-0002-8568-1110
authors.initials: T
authors.lastname: Tzanov
mesh_terms: D000900:Anti-Bacterial Agents; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli; D006090:Gram-Negative Bacteria; D008826:Microbial Sensitivity Tests; D014640:Vancomycin
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: Vancomycin; antibiotic nanospheres; antibiotic resistance; biofilms; sonochemistry