3 years ago

Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets [Applied Biological Sciences]

Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets [Applied Biological Sciences]
Yu Wang, John M. Thompson, Alexander J. Tzomides, Carly A. Dillen, Alyssa G. Ashbaugh, Lily I. Cheng, Taylor S. Cohen, Andrew S. Tsai, Christine Tkaczyk, Roger V. Ortines, Robert J. Miller, Lloyd S. Miller, C. Kendall Stover, David R. Helfer, Nathan K. Archer, Haiyun Liu, Bret R. Sellman

Infection is a major complication of implantable medical devices, which provide a scaffold for biofilm formation, thereby reducing susceptibility to antibiotics and complicating treatment. Hematogenous implant-related infections following bacteremia are particularly problematic because they can occur at any time in a previously stable implant. Herein, we developed a model of hematogenous infection in which an orthopedic titanium implant was surgically placed in the legs of mice followed 3 wk later by an i.v. exposure to Staphylococcus aureus. This procedure resulted in a marked propensity for a hematogenous implant-related infection comprised of septic arthritis, osteomyelitis, and biofilm formation on the implants in the surgical legs compared with sham-operated surgical legs without implant placement and with contralateral nonoperated normal legs. Neutralizing human monoclonal antibodies against α-toxin (AT) and clumping factor A (ClfA), especially in combination, inhibited biofilm formation in vitro and the hematogenous implant-related infection in vivo. Our findings suggest that AT and ClfA are pathogenic factors that could be therapeutically targeted against S. aureus hematogenous implant-related infections.

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