title: Silver nanoparticles strongly enhance and restore bactericidal activity of inactive antibiotics against multiresistant Enterobacteriaceae.
abstract: Bacterial resistance to conventional antibiotics is currently one of the most important healthcare issues, and has serious negative impacts on medical practice. This study presents a potential solution to this problem, using the strong synergistic effects of antibiotics combined with silver nanoparticles (NPs). Silver NPs inhibit bacterial growth via a multilevel mode of antibacterial action at concentrations ranging from a few ppm to tens of ppm. Silver NPs strongly enhanced antibacterial activity against multiresistant, β-lactamase and carbapenemase-producing Enterobacteriaceae when combined with the following antibiotics: cefotaxime, ceftazidime, meropenem, ciprofloxacin and gentamicin. All the antibiotics, when combined with silver NPs, showed enhanced antibacterial activity at concentrations far below the minimum inhibitory concentrations (tenths to hundredths of one ppm) of individual antibiotics and silver NPs. The enhanced activity of antibiotics combined with silver NPs, especially meropenem, was weaker against non-resistant bacteria than against resistant bacteria. The double disk synergy test showed that bacteria produced no β-lactamase when treated with antibiotics combined with silver NPs. Low silver concentrations were required for effective enhancement of antibacterial activity against multiresistant bacteria. These low silver concentrations showed no cytotoxic effect towards mammalian cells, an important feature for potential medical applications.
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic. Electronic address: ales.panacek@upol.cz.
authors.forename: Aleš
authors.initials: A
authors.lastname: Panáček
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Smékalová
authors.affiliation: Department of Microbiology, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 5, 775 15 Olomouc, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Večeřová
authors.affiliation: Department of Microbiology, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 5, 775 15 Olomouc, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Bogdanová
authors.affiliation: Department of Microbiology, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 5, 775 15 Olomouc, Czech Republic.
authors.forename: Magdaléna
authors.initials: M
authors.lastname: Röderová
authors.affiliation: Department of Microbiology, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 5, 775 15 Olomouc, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Kolář
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Kilianová
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Šárka
authors.initials: Š
authors.lastname: Hradilová
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Froning
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Experimental Physics, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Markéta
authors.initials: M
authors.lastname: Havrdová
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Robert
authors.initials: R
authors.lastname: Prucek
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Zbořil
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Libor
authors.initials: L
authors.lastname: Kvítek
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002439:Cefotaxime / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000235:genetics; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D015870:Gene Expression; D005839:Gentamicins / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D000077731:Meropenem; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D008826:Microbial Sensitivity Tests; D012834:Silver / Q000494:pharmacology*; D013845:Thienamycins / Q000494:pharmacology; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D013845:Thienamycins; D012834:Silver; D002939:Ciprofloxacin; D002442:Ceftazidime; D001618:beta-Lactamases; D000077731:Meropenem; D002439:Cefotaxime
keywords: Antibiotic; Cytotoxicity; Resistant bacteria; Silver nanoparticle; Synergism