title: Near-infrared fluorescence imaging as an alternative to bioluminescent bacteria to monitor biomaterial-associated infections.
abstract: Biomaterial-associated infection is one of the most common complications related to the implantation of any biomedical device. Several in vivo imaging platforms have emerged as powerful diagnostic tools to longitudinally monitor biomaterial-associated infections in small animal models. In this study, we directly compared two imaging approaches: bacteria engineered to produce luciferase to generate bioluminescence and reactive oxygen species (ROS) imaging of the inflammatory response associated with the infected implant. We performed longitudinal imaging of bioluminescence associated with bacteria strains expressing plasmid-integrated luciferase driven by different promoters or a strain with the luciferase gene integrated into the chromosome. These luminescent strains provided an adequate signal for acute (0-4 days) monitoring of the infection, but the bioluminescence signal decreased over time and leveled off at 7 days post-implantation. This loss in the bioluminescence signal was attributed to changes in the metabolic activity of the bacteria. In contrast, near-infrared fluorescence imaging of ROS associated with inflammation to the implant provided sensitive and dose-dependent signals of biomaterial-associated bacteria. ROS imaging exhibited higher sensitivity than the bioluminescence imaging and was independent of the bacteria strain. Near-infrared fluorescence imaging of inflammatory responses represents a powerful alternative to bioluminescence imaging for monitoring biomaterial-associated bacterial infections.
authors.affiliation: Centro de Investigaciones Biológicas, CSIC, Madrid 28040, Spain.
authors.forename: Nina
authors.initials: N
authors.lastname: Dinjaski
authors.affiliation: Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0363, USA.
authors.forename: Shalu
authors.initials: S
authors.lastname: Suri
authors.affiliation: Instituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31006 Pamplona, Spain.
authors.forename: Jaione
authors.initials: J
authors.lastname: Valle
authors.affiliation: Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0363, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lehman
authors.affiliation: Instituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31006 Pamplona, Spain.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Lasa
authors.affiliation: Centro de Investigaciones Biológicas, CSIC, Madrid 28040, Spain.
authors.forename: María Auxiliadora
authors.initials: MA
authors.lastname: Prieto
authors.affiliation: Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0363, USA. Electronic address: andres.garcia@me.gatech.edu.
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects*; D005453:Fluorescence; D007239:Infections / Q000209:etiology*; D051379:Mice; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials
keywords: Bioluminescence; Biomaterial-associated infection; Near infrared fluorescence; Noninvasive monitoring; Staphylococcus aureus