Mouse model of Gram-negative prosthetic joint infection reveals therapeutic targets

• DOI: 10.1172/jci.insight.121737
• Publication Date: 2018-09-05T15:02:36Z
• Authors: John M. Thompson; Robert J. Miller; Alyssa G. Ashbaugh; Carly A. Dillen; Julie E. Pickett; Yu Wang; Roger V. Ortines; Robert S. Sterling; Kevin P. Francis; Nicholas M. Bernthal; Taylor S. Cohen; Christine Tkaczyk; Li Yu; C. Kendall Stover; Antonio DiGiandom...; Bret R. Sellman; Daniel L.J. Thorek; Lloyd S. Miller
• Keywords: Joint infections

Bacterial biofilm infections of implantable medical devices decrease the effectiveness antibiotics, creating difficult-to-treat chronic infections. Prosthetic joint (PJI) are particularly problematic because they require prolonged antibiotic courses and reoperations to remove replace infected prostheses. Current models study PJI focus on Gram-positive bacteria, but Gram-negative (GN-PJI) increasingly common often more difficult treat, with worse clinical outcomes. Herein, we sought develop a mouse model GN-PJI investigate pathogenesis these identify potential therapeutic targets. An orthopedic-grade titanium implant was surgically placed in femurs mice, followed by infection knee Pseudomonas aeruginosa or Escherichia coli. We found that vitro biofilm-producing activity associated development an vivo orthopedic characterized bacterial bone/joint tissue, formation implants, reactive bone changes, inflammatory immune cell infiltrates. In addition, bispecific antibody targeting P. virulence factors (PcrV Psl exopolysaccharide) reduced burden vivo. Taken together, our findings provide preclinical suggest biofilm-associated antigens.