title: Real-time monitoring of bacterial infection in vivo: development of bioluminescent staphylococcal foreign-body and deep-thigh-wound mouse infection models.
abstract: Staphylococcal infections associated with catheter and prosthetic implants are difficult to eradicate and often lead to chronic infections. Development of novel antibacterial therapies requires simple, reliable, and relevant models for infection. Using bioluminescent Staphylococcus aureus, we have adapted the existing foreign-body and deep-wound mouse models of staphylococcal infection to allow real-time monitoring of the bacterial colonization of catheters or tissues. This approach also enables kinetic measurements of bacterial growth and clearance in each infected animal. Persistence of infection was observed throughout the course of the study until termination of the experiment at day 16 in a deep-wound model and day 21 in the foreign-body model, providing sufficient time to test the effects of antibacterial compounds. The usefulness of both animal models was assessed by using linezolid as a test compound and comparing bioluminescent measurements to bacterial counts. In the foreign-body model, a three-dose antibiotic regimen (2, 5, and 24 h after infection) resulted in a decrease in both luminescence and bacterial counts recovered from the implant compared to those of the mock-treated infected mice. In addition, linezolid treatment prevented the formation of subcutaneous abscesses, although it did not completely resolve the infection. In the thigh model, the same treatment regimen resulted in complete resolution of the luminescent signal, which correlated with clearance of the bacteria from the thighs.
authors.affiliation: Merck and Co, Inc, West Point, Pennsylvania 19486, USA. nelly_kuklin@merck.com
authors.forename: Nelly A
authors.initials: NA
authors.lastname: Kuklin
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Pancari
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Tobery
authors.forename: Leslie
authors.initials: L
authors.lastname: Cope
authors.forename: Jesse
authors.initials: J
authors.lastname: Jackson
authors.forename: Charles
authors.initials: C
authors.lastname: Gill
authors.forename: Karen
authors.initials: K
authors.lastname: Overbye
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Francis
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Donna
authors.initials: D
authors.lastname: Montgomery
authors.forename: Annaliesa S
authors.initials: AS
authors.lastname: Anderson
authors.forename: William
authors.initials: W
authors.lastname: McClements
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
mesh_terms: D000038:Abscess / Q000382:microbiology; D000081:Acetamides / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002404:Catheterization; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D005260:Female; D005547:Foreign Bodies / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D000069349:Linezolid; D008163:Luminescent Measurements; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000473:pathology; D023303:Oxazolidinones / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000254:growth & development / Q000378:metabolism; D013848:Thigh / Q000473:pathology; D013997:Time Factors; D014946:Wound Infection / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid