title: Autoinducer-2 analogs and electric fields - an antibiotic-free bacterial biofilm combination treatment.
abstract: Bacterial biofilms are a common cause of chronic medical implant infections. Treatment and eradication of biofilms by conventional antibiotic therapy has major drawbacks including toxicity and side effects associated with high-dosage antibiotics. Additionally, administration of high doses of antibiotics may facilitate the emergence of antibiotic resistant bacteria. Thus, there is an urgent need for the development of treatments that are not based on conventional antibiotic therapies. Presented herein is a novel bacterial biofilm combination treatment independent of traditional antibiotics, by using low electric fields in combination with small molecule inhibitors of bacterial quorum sensing - autoinducer-2 analogs. We investigate the effect of this treatment on mature Escherichia coli biofilms by application of an alternating and offset electric potential in combination with the small molecule inhibitor for 24 h using both macro and micro-scale devices. Crystal violet staining of the macro-scale biofilms shows a 46 % decrease in biomass compared to the untreated control. We demonstrate enhanced treatment efficacy of the combination therapy using a high-throughput polydimethylsiloxane-based microfluidic biofilm analysis platform. This microfluidic flow cell is designed to reduce the growth variance of in vitro biofilms while providing an integrated control, and thus allows for a more reliable comparison and evaluation of new biofilm treatments on a single device. We utilize linear array charge-coupled devices to perform real-time tracking of biomass by monitoring changes in optical density. End-point confocal microscopy measurements of biofilms treated with the autoinducer analog and electric fields in the microfluidic device show a 78 % decrease in average biofilm thickness in comparison to the negative controls and demonstrate good correlation with real-time optical density measurements. Additionally, the combination treatment showed 76 % better treatment efficacy compared to conventional antibiotic therapy. Taken together these results suggest that the antibiotic-free combination treatment described here may provide an effective alternative to traditional antibiotic therapies against bacterial biofilm infections. Use of this combination treatment in the medical and environmental fields would alleviate side effects associated with high-dosage antibiotic therapies, and reduce the rise of antibiotic-resistant bacteria.
authors.affiliation: MEMS Sensors and Actuators Laboratory, Institute for Systems Research, University of Maryland, 2201 J.M. Patterson Building, College Park, MD, 20742, USA. dr.sowmya.subramanian@gmail.com.|Department of Electrical and Computer Engineering, University of Maryland, 2435 A.V. Williams Building, College Park, MD, 20742, USA. dr.sowmya.subramanian@gmail.com.
authors.forename: Sowmya
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: MEMS Sensors and Actuators Laboratory, Institute for Systems Research, University of Maryland, 2201 J.M. Patterson Building, College Park, MD, 20742, USA.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Gerasopoulos
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, 0107 Chemistry Building, College Park, MD, 20742, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, 0107 Chemistry Building, College Park, MD, 20742, USA.
authors.forename: Herman O
authors.initials: HO
authors.lastname: Sintim
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, 2330 Jeong H. Kim Engineering Building, College Park, MD, 20742, USA.|Department of Chemical and Biomolecular Engineering, University of Maryland, 2113 Chemical & Nuclear Engineering Building, College Park, MD, 20742, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Bentley
authors.affiliation: MEMS Sensors and Actuators Laboratory, Institute for Systems Research, University of Maryland, 2201 J.M. Patterson Building, College Park, MD, 20742, USA. ghodssi@umd.edu.|Department of Electrical and Computer Engineering, University of Maryland, 2435 A.V. Williams Building, College Park, MD, 20742, USA. ghodssi@umd.edu.|Fischell Department of Bioengineering, University of Maryland, 2330 Jeong H. Kim Engineering Building, College Park, MD, 20742, USA. ghodssi@umd.edu.
authors.forename: Reza
authors.initials: R
authors.lastname: Ghodssi
mesh_terms: D018441:Biofilms / Q000187:drug effects*; D004560:Electricity; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006714:Homoserine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D056656:Lab-On-A-Chip Devices; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D018613:Microscopy, Confocal; D053038:Quorum Sensing / Q000187:drug effects
chemical_list: D007783:Lactones; C091088:N-octanoylhomoserine lactone; D006714:Homoserine
keywords: Autoinducer analogs; Bioelectric effect; Biofilms; Micro-systems; Microfluidics; Polydimethylsiloxane; Quorum sensing