title: Mouse model of chronic post-arthroplasty infection: noninvasive in vivo bioluminescence imaging to monitor bacterial burden for long-term study.
abstract: Post-arthroplasty infections are a devastating problem in orthopaedic surgery. While acute infections can be treated with a single stage washout and liner exchange, chronic infections lead to multiple reoperations, prolonged antibiotic courses, extended disability, and worse clinical outcomes. Unlike previous mouse models that studied an acute infection, this work aimed to develop a model of a chronic post-arthroplasty infection. To achieve this, a stainless steel implant in the knee joints of mice was inoculated with a bioluminescent Staphylococcus aureus strain (1 × 10(2) -1 × 10(4) colony forming units, CFUs) and in vivo imaging was used to monitor the bacterial burden for 42 days. Four different S. aureus strains were compared in which the bioluminescent construct was integrated in an antibiotic selection plasmid (ALC2906), the bacterial chromosome (Xen29 and Xen40), or a stable plasmid (Xen36). ALC2906 had increased bioluminescent signals through day 10, after which the signals became undetectable. In contrast, Xen29, Xen40, and Xen36 had increased bioluminescent signals through 42 days with the highest signals observed with Xen36. ALC2906, Xen29, and Xen40 induced significantly more inflammation than Xen36 as measured by in vivo enhanced green fluorescence protein (EGFP)-neutrophil flourescence of LysEGFP mice. All four strains induced comparable biofilm formation as determined by variable-pressure scanning electron microscopy. Using a titanium implant, Xen36 had higher in vivo bioluminescence signals than Xen40 but had similar biofilm formation and adherent bacteria. In conclusion, Xen29, Xen40, and especially Xen36, which had stable bioluminescent constructs, are feasible for long-term in vivo monitoring of bacterial burden and biofilm formation to study chronic post-arthroplasty infections and potential antimicrobial interventions.
authors.affiliation: Orthopaedic Hospital Research Center, Orthopaedic Hospital Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Pribaz
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Bernthal
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Billi
authors.forename: John S
authors.initials: JS
authors.lastname: Cho
authors.forename: Romela Irene
authors.initials: RI
authors.lastname: Ramos
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Ambrose L
authors.initials: AL
authors.lastname: Cheung
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Francis
authors.forename: Lloyd S
authors.initials: LS
authors.lastname: Miller
mesh_terms: D000818:Animals; D001170:Arthritis, Infectious / Q000382:microbiology*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D058491:Bacterial Load; D018441:Biofilms; D002908:Chronic Disease; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D007595:Joint Prosthesis / Q000382:microbiology*; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology; D011183:Postoperative Complications / Q000382:microbiology*; D013211:Staphylococcus aureus; D014025:Titanium
chemical_list: D049452:Green Fluorescent Proteins; D014025:Titanium