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Wang, Yu; Cheng, Lily I.; Helfer, David R.; Ashbaugh, Alyssa G.; Miller, Robert J.; Tzomides, Alexander J.; Thompson, John M.; Ortines, Roger V.; Tsai, Andrew S.; Liu, Haiyun; Dillen, Carly A.; Archer, Nathan K.; Cohen, Taylor S.; Tkaczyk, Christine; Stover, C. Kendall; Sellman, Bret R.; Miller, Lloyd S.
Proceedings of the National Academy of Sciences, 06/2017, Letnik: 114, Številka: 26Journal Article
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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