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

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 Saureus hematogenous implant-related infections.

• Authors: 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
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 114 Issue 26 Pg. E5094-E5102 (06 27 2017) ISSN: 1091-6490 [Electronic] United States
• PMID: 28607050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bacterial
• Antibodies, Neutralizing
• Titanium

Topics

• Animals
• Antibodies, Bacterial (pharmacology)
• Antibodies, Neutralizing (pharmacology)
• Arthritis, Infectious (drug therapy, etiology, microbiology)
• Biofilms (drug effects)
• Disease Models, Animal
• Humans
• Implants, Experimental (microbiology)
• Male
• Mice
• Osteomyelitis (drug therapy, etiology, microbiology)
• Staphylococcal Infections (drug therapy, etiology, microbiology)
• Staphylococcus aureus (physiology)
• Titanium