title: Sensitizing Pseudomonas aeruginosa to antibiotics by electrochemical disruption of membrane functions.
abstract: Recently, we reported synergistic effects between 70 μA/cm(2) direct current and tobramycin in killing Pseudomonas aeruginosa PAO1 persister cells, a phenomenon we named electrochemical control of persister cells (ECCP; Niepa et al. Biomaterials 33: 7356-7365, 2012). To understand the mechanism of ECCP, the effects of electrochemical treatments mediated via stainless steel 304 and carbon electrodes on P. aeruginosa PAO1 were systematically compared using complementary approaches in this study. Electron microscopic analysis revealed that μA/cm(2) level direct current (DC) caused substantial changes in the structure and membrane integrity of P. aeruginosa PAO1 cells. DC treatments using SS304 electrodes induced cell lysis, while the same level of DC generated using carbon electrodes led to aggregation of intracellular proteins and increased permeabilization of P. aeruginosa PAO1 cells to antibiotics. The profound effects of DC on the physiology of persister cells were corroborated with DNA microarray analysis, which revealed the induction of genes associated with pyocin production and SOS response in DC-treated persister cells. Interestingly, sequential treatment using DC mediated with carbon electrodes followed by tobramycin was found more effective than concurrent treatment; and total eradication of persister cells was achieved.
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA; Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Tagbo H R
authors.initials: TH
authors.lastname: Niepa
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA; Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Snepenger
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA; Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA; Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Shiril
authors.initials: S
authors.lastname: Sivan
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA; Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Gilbert
authors.affiliation: J. Craig Venter Institute, La Jolla, CA 92037, USA; Human Longevity, Inc., San Diego, CA 92121, USA.
authors.forename: Marcus B
authors.initials: MB
authors.lastname: Jones
authors.affiliation: Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA; Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA; Department of Civil and Environmental Engineering, Syracuse University, Syracuse, NY 13244, USA; Department of Biology, Syracuse University, Syracuse, NY 13244, USA. Electronic address: dren@syr.edu.
authors.forename: Dacheng
authors.initials: D
authors.lastname: Ren
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane; D004563:Electrochemistry; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents
keywords: Electrodes; Gene expression; Membrane; Persister cells; SEM-EDS; TEM