Acinetobacter quorum sensing contributes to inflammation-induced inhibition of orthopaedic implant osseointegration
1 Department of Orthopaedics, Case Western Reserve University, Cleveland, OH, 44106, USA
2 Department of Orthopaedics, Yokohama City University, Yokohama, Kanagawa, 236-0004, Japan
3 Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, 44106, USA
4 Medical Service and GRECC, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, 44106, USA
5 Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA
6 CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, OH, 44106, USA
7 Department of Mechanical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA
8 Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30307, USA
9 Research Service, Atlanta Veterans Affairs Medical Center, Decatur, GA, 30033, USA
10 Department of Radiology, Case Western Reserve University, Cleveland, OH, 44106, USA
11 Department of Orthopaedic Surgery and Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, 44106, USA
12 Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, 44106, USA
Abstract
Implant infection impairs osseointegration of orthopaedic implants by inducing inflammation. Acinetobacter spp. are increasingly prevalent multi-drug resistant bacteria that can cause osteomyelitis. Acinetobacter spp. can also cause inflammation and thereby inhibit osseointegration in mice. The purpose of the present study was to investigate the role of quorum sensing in this context. Therefore, wild-type bacteria were compared with an isogenic abaI mutant defective in quorum sensing in a murine osseointegration model. The abaI quorum- sensing mutant affected significantly less osseointegration and interleukin (IL) 1β levels, without detectably altering other pro-inflammatory cytokines. Wild-type bacteria had fewer effects on IL1 receptor (IL1R)−/− mice. These results indicated that quorum sensing in Acinetobacter spp. contributed to IL1β induction and the resultant inhibition of osseointegration in mice. Moreover, targeting the Gram-negative acyl-homoserine lactone quorum sensing may be particularly effective for patients with Acinetobacter spp. infections.
Graphical Abstract
Keywords
- Artificial ligament
- polyethylene terephthalate
- profiled filaments
- calcium phosphate
- ligamentisation
- bone formation
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