title: Synergy between tobramycin and trivalent chromium ion in electrochemical control of Pseudomonas aeruginosa.
abstract: We recently demonstrated that the effectiveness of tobramycin (Tob), an aminoglycoside, against antibiotic-tolerant persister cells of Pseudomonas aeruginosa can be enhanced by electrochemical factors generated from direct currents (DC). Supplementation of Ni(II), Cr(III) and Fe(II) during carbon-mediated DC treatment revealed that these metal cations promote killing of persister cells in the presence of tobramycin, which led to our hypothesis that specific interactions between Tob and some metal ions contribute to the synergistic killing of persister cells. In this study, the interactions between selected metal cations and Tob were investigated using (1)H-(13)C HSQC NMR. Increase in the concentration of Cr(III) (in the form of [CrCl2(H2O)4](+)) in solutions containing Tob was found to shift the HSQC NMR peaks of Tob to new positions, suggesting the formation of a Cr(III)-Tob complex. Crystal field effects and electrochemical properties of the complex were further studied using UV-visible spectroscopy and cyclic voltammetry, which led to the finding that the Cr(III)-Tob complex has increased affinity with negatively charged nucleic acids. These findings are helpful for understanding the mechanism of electrochemical control of bacterial cells and for developing more effective antimicrobial therapies based on aminoglycosides and electrochemical species released from various metallic biomaterials.
  
  
  
  Medical device associated infections present a major challenge to healthcare and the quality of life of affected individuals. This problem is further exacerbated by the emergence of multidrug resistant pathogens. Thus, alternative methods for microbial control are urgently needed. Recently, we reported synergy between tobramycin and low-level electrochemical currents generated using stainless steel electrodes in killing bacterial persister cells, a dormant population with high-level intrinsic tolerance to antibiotics. In this article, we describe how electrically-induced interaction between aminoglycosides and certain metal cations enhance the potency of tobramycin in bacterial killing. The findings will help design new methods for controlling infections through electrochemical disruption of cellular function and associated drug resistance.
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, United States; Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, United States.
authors.forename: Tagbo H R
authors.initials: TH
authors.lastname: Niepa
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, United States; Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, United States.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, United States; Department of Chemistry, Syracuse University, Syracuse, NY 13244, United States.
authors.forename: James C
authors.initials: JC
authors.lastname: Dabrowiak
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, United States; Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, United States.
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Gilbert
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, United States; Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, United States; Department of Civil and Environmental Engineering, Syracuse University, Syracuse, NY 13244, United States; Department of Biology, Syracuse University, Syracuse, NY 13244, United States. Electronic address: dren@syr.edu.
authors.forename: Dacheng
authors.initials: D
authors.lastname: Ren
mesh_terms: D002857:Chromium / Q000819:agonists / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004357:Drug Synergism; D011550:Pseudomonas aeruginosa / Q000254:growth & development*; D014031:Tobramycin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002857:Chromium; D014031:Tobramycin
keywords: Aminoglycoside; Bacteria; Binding; Chromium; Electrochemical control; Tobramycin