Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets

Yu Wang, Lily I. Cheng, David R. Helfer, Alyssa G. Ashbaugh, Robert J. Miller, Alexander J. Tzomides, John M. Thompson, Roger V. Ortines, Andrew S. Tsai, Haiyun Liu, Carly A. Dillen, Nathan K. Archer, Taylor S. Cohen, Christine Tkaczyk, C. Kendall Stover, Bret R. Sellman, Lloyd S. Miller

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E5094-E5102
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number26
DOIs
StatePublished - Jun 27 2017

Keywords

  • Biofilm
  • Hematogenous
  • Implant
  • Orthopedic
  • Staphylococcus aureus

ASJC Scopus subject areas

  • General

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  • Cite this

    Wang, Y., Cheng, L. I., Helfer, D. R., Ashbaugh, A. G., Miller, R. J., Tzomides, A. J., Thompson, J. M., Ortines, R. V., Tsai, A. S., Liu, H., Dillen, C. A., Archer, N. K., Cohen, T. S., Tkaczyk, C., Stover, C. K., Sellman, B. R., & Miller, L. S. (2017). Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets. Proceedings of the National Academy of Sciences of the United States of America, 114(26), E5094-E5102. https://doi.org/10.1073/pnas.1703427114