Real time noninvasive monitoring of contaminating bacteria in a soft tissue implant infection model.

Infection is the main cause of biomaterials-related failure. A simple technique to test in-vivo new antimicrobial and/or nonadhesive implant coatings is unavailable. Current in vitro methods for studying bacterial adhesion and growth on biomaterial surfaces lack the influence of the host immune system. Most in vivo methods to study biomaterials-related infections routinely involve implant-removal, preventing comprehensive longitudinal monitoring. In vivo imaging circumvents these drawbacks and is based on the use of noninvasive optical imaging of bioluminescent bacteria. Staphylococcus aureus Xen29 is genetically modified to be stably bioluminescent, by the introduction of a modified full lux operon onto its chromosome. Surgical meshes with adhering S. aureus Xen29 were implanted in mice and bacterial growth and spread into the surrounding tissue was monitored longitudinally from bioluminescence with a highly sensitive CCD camera. Distinct spatiotemporal bioluminescence patterns, extending beyond the mesh area into surrounding tissues were observed. After 10 days, the number of living organisms isolated from explanted meshes was found to correlate with bioluminescence prior to sacrifice of the animals. Therefore, it is concluded that in vivo imaging using bioluminescent bacteria is ideally suited to study antimicrobial coatings taking into account the host immune system. In addition, longitudinal monitoring of infection in one animal will significantly reduce the number of experiments and animals.

[1]  Kathrin U. Jansen,et al.  Real-Time Monitoring of Bacterial Infection In Vivo: Development of Bioluminescent Staphylococcal Foreign-Body and Deep-Thigh-Wound Mouse Infection Models , 2003, Antimicrobial Agents and Chemotherapy.

[2]  P. Iversen,et al.  Validation of a Noninvasive, Real-Time Imaging Technology Using Bioluminescent Escherichia coli in the Neutropenic Mouse Thigh Model of Infection , 2001, Antimicrobial Agents and Chemotherapy.

[3]  G. Smith,et al.  Biofilm culture of Pseudomonas aeruginosa expressing lux genes as a model to study susceptibility to antimicrobials. , 2001, FEMS microbiology letters.

[4]  David K. Stevenson,et al.  Bioluminescent indicators in living mammals , 1998, Nature Medicine.

[5]  A. Park,et al.  Laparoscopic Repair of Ventral Hernias: Nine Years’ Experience With 850 Consecutive Hernias , 2003, Annals of surgery.

[6]  Lothar Lilge,et al.  In Vivo Study of the Inflammatory Modulating Effects of Low-level Laser Therapy on iNOS Expression Using Bioluminescence Imaging , 2005, Photochemistry and photobiology.

[7]  Kevin P. Francis,et al.  Monitoring Bioluminescent Staphylococcus aureusInfections in Living Mice Using a Novel luxABCDEConstruct , 2000, Infection and Immunity.

[8]  Q. Myrvik,et al.  Infections from biomaterials and implants: a race for the surface. , 1988, Medical progress through technology.

[9]  R. Darouiche,et al.  Treatment of infections associated with surgical implants. , 2004, The New England journal of medicine.

[10]  Marvin D Nelson,et al.  Multimodal Imaging Analysis of Tumor Progression and Bone Resorption in a Murine Cancer Model , 2006, Journal of computer assisted tomography.

[11]  Kevin P. Francis,et al.  Rapid Direct Method for Monitoring Antibiotics in a Mouse Model of Bacterial Biofilm Infection , 2003, Antimicrobial Agents and Chemotherapy.

[12]  B. Klosterhalfen,et al.  Do multifilament alloplastic meshes increase the infection rate? Analysis of the polymeric surface, the bacteria adherence, and the in vivo consequences in a rat model. , 2002, Journal of biomedical materials research.

[13]  H. C. van der Mei,et al.  The phenomenon of infection with abdominal wall reconstruction. , 2007, Biomaterials.

[14]  J. Leiva,et al.  A simple infection model using pre‐colonized implants to reproduce rat chronic Staphylococcus aureus osteomyelitis and study antibiotic treatment , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[15]  J. Feijen,et al.  Positively charged biomaterials exert antimicrobial effects on gram-negative bacilli in rats. , 2003, Biomaterials.

[16]  C. R. Lowe,et al.  Optimisation of polymeric surface pre‐treatment to prevent bacterial biofilm formation for use in microfluidics , 2004, Journal of molecular recognition : JMR.

[17]  J. Dankert,et al.  Peri-Implant Tissue Is an Important Niche for Staphylococcus epidermidis in Experimental Biomaterial-Associated Infection in Mice , 2006, Infection and Immunity.

[18]  D. Jenkins,et al.  Bioluminescent imaging (BLI) to improve and refine traditional murine models of tumor growth and metastasis , 2004, Clinical & Experimental Metastasis.

[19]  M. Freitag,et al.  Deep prosthesis infection in incisional hernia repair: predictive factors and clinical outcome. , 2001, The European journal of surgery = Acta chirurgica.

[20]  Kevin Francis,et al.  Direct Continuous Method for Monitoring Biofilm Infection in a Mouse Model , 2003, Infection and Immunity.

[21]  B. Rice,et al.  In vivo imaging of light-emitting probes. , 2001, Journal of biomedical optics.

[22]  C. de la Cuesta,et al.  Laparoscopic Treatment of Ventral Abdominal Wall Hernias: Preliminary Results in 100 Patients , 2000, JSLS : Journal of the Society of Laparoendoscopic Surgeons.