Mouse Model of Hematogenous Implant-related Biofilm Infection Reveals Therapeutic Targets

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2017 Jun 14

PMID 28607050

Citations 57

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

Affiliations

Soon will be listed here.

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 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 hematogenous implant-related infections.

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