title: Antibacterial activity of a new broad-spectrum antibiotic covalently bound to titanium surfaces.
abstract: Biofilm-associated infections, particularly those caused by Staphylococcus aureus, are a major cause of implant failure. Covalent coupling of broad-spectrum antimicrobials to implants is a promising approach to reduce the risk of infections. In this study, we developed titanium substrates on which the recently discovered antibacterial agent SPI031, a N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol, was covalently linked (SPI031-Ti). We found that SPI031-Ti substrates prevent biofilm formation of S. aureus and Pseudomonas aeruginosa in vitro, as quantified by plate counting and fluorescence microscopy. To test the effectiveness of SPI031-Ti substrates in vivo, we used an adapted in vivo biomaterial-associated infection model in mice in which SPI031-Ti substrates were implanted subcutaneously and subsequently inoculated with S. aureus. Using this model, we found a significant reduction in biofilm formation (up to 98%) on SPI031-Ti substrates compared to control substrates. Finally, we demonstrated that the functionalization of the titanium surfaces with SPI031 did not influence the adhesion and proliferation of human cells important for osseointegration and bone repair. In conclusion, these data demonstrate the clinical potential of SPI031 to be used as an antibacterial coating for implants, thereby reducing the incidence of implant-associated infections. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2191-2198, 2016.
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20 box 2460, 3001 Leuven, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: Gerits
authors.affiliation: Department of Molecular Microbiology, VIB, KU Leuven, Kasteelpark Arenberg 31 box 2438, 3001 Leuven, Belgium.|Laboratory of Molecular Cell Biology, KU Leuven, Kasteelpark Arenberg 31 box 2438, 3001 Leuven, Belgium.
authors.forename: Soňa
authors.initials: S
authors.lastname: Kucharíková
authors.affiliation: Department of Molecular Microbiology, VIB, KU Leuven, Kasteelpark Arenberg 31 box 2438, 3001 Leuven, Belgium.|Laboratory of Molecular Cell Biology, KU Leuven, Kasteelpark Arenberg 31 box 2438, 3001 Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Dijck
authors.affiliation: Hemoteq AG, Adenauerstraße 15, 52146 Wuerselen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Erdtmann
authors.affiliation: Department of Structure and Material Design, SP Food and Bioscience, Box 5401, 402 29 Gothenburg, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Krona
authors.affiliation: Department of Structure and Material Design, SP Food and Bioscience, Box 5401, 402 29 Gothenburg, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Lövenklev
authors.affiliation: Educell Ltd, Prevale 9, 1236 Trzin, Slovenia.|Faculty of Medicine, Institute of Cell Biology, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Fröhlich
authors.affiliation: Educell Ltd, Prevale 9, 1236 Trzin, Slovenia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Dovgan
authors.affiliation: Biotech International, Allées de Craponne 305, 13300 Salon-de-Provence, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Impellizzeri
authors.affiliation: Department of Materials Engineering (MTM), KU Leuven, Kasteelpark Arenberg 44 box 2450, 3001 Leuven, Belgium.
authors.forename: Annabel
authors.initials: A
authors.lastname: Braem
authors.affiliation: Department of Materials Engineering (MTM), KU Leuven, Kasteelpark Arenberg 44 box 2450, 3001 Leuven, Belgium.
authors.forename: Jef
authors.initials: J
authors.lastname: Vleugels
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20 box 2460, 3001 Leuven, Belgium.
authors.forename: Stijn C A
authors.initials: SC
authors.lastname: Robijns
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20 box 2460, 3001 Leuven, Belgium.
authors.forename: Hans P
authors.initials: HP
authors.lastname: Steenackers
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20 box 2460, 3001 Leuven, Belgium.
authors.forename: Jozef
authors.initials: J
authors.lastname: Vanderleyden
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20 box 2460, 3001 Leuven, Belgium.
authors.forename: Katrijn
authors.initials: K
authors.lastname: De Brucker
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20 box 2460, 3001 Leuven, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Thevissen
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20 box 2460, 3001 Leuven, Belgium.|Department of Plant Systems Biology, VIB, Technologiepark 927, 9052 Ghent, Belgium.
authors.forename: Bruno P A
authors.initials: BP
authors.lastname: Cammue
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20 box 2460, 3001 Leuven, Belgium.|Department of Life Science Technologies, imec, Smart Systems and Emerging Technologies Unit, Kapeldreef 75, 3001 Leuven, Belgium.
authors.forename: Maarten
authors.initials: M
authors.lastname: Fauvart
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20 box 2460, 3001 Leuven, Belgium.
authors.forename: Natalie
authors.initials: N
authors.lastname: Verstraeten
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20 box 2460, 3001 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Michiels
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D016459:Prosthesis-Related Infections / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D014025:Titanium
chemical_list: D000890:Anti-Infective Agents; D002227:Carbazoles; C000622119:SPI031; D014025:Titanium
keywords: Pseudomonas aeruginosa; SPI031; Staphylococcus aureus; biofilm; titanium