Septic arthritis in an in vivo murine model induced by Staphylococcus aureus: a comparison between actions of the haemolysin toxin and the effects of the host immune response

Bone & Joint Research

article

Rhys G. E. Clement¹  Andrew C. Hall²  Seng J. Wong³  Sarah E. M. Howie⁴  A. Hamish R. W. Simpson¹ 

[1] Department of Orthopaedics and Trauma, University of Edinburgh;Deanery of Biomedical Sciences, The University of Edinburgh;Department of Orthopaedic Surgery, Singapore General Hospital;MRC Centre for Inflammation Research, University of Edinburgh

关键词: Septic arthritis;    Hla toxin;    Cartilage;    Chondrocyte;    Staphylococcus aureus;    septic arthritis;    murine models;    chondrocytes;    Hla;    strains;    cartilage;    toxins;    infection;    bacteria;   

DOI  :  10.1302/2046-3758.119.BJR-2022-0016.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsStaphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection.MethodsAdult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 107 colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling.ResultsChondrocyte death was greater with 8325-4 (96.2% (SD 5.5%); p < 0.001) than DU1090 (28.9% (SD 16.0%); p = 0.009) and both were higher than controls (3.8% (SD 1.2%)). Histology revealed cartilage/bone damage with 8325-4 or DU1090 compared to controls (p = 0.010). Both infected groups lost weight (p = 0.006 for both) and experienced limb swelling (p = 0.043 and p = 0.018, respectively). Joints inoculated with bacteria showed significant alterations in gait cycle with a decreased stance phase, increased swing phase, and a corresponding decrease in swing speed.ConclusionMurine joints inoculated with Hla-producing 8325-4 experienced significantly more chondrocyte death than those with DU1090, which lack the toxin. This was despite similar immune responses, indicating that Hla was the major cause of chondrocyte death. Hla-deficient DU1090 also elevated chondrocyte death compared to controls, suggesting a smaller additional deleterious role of the immune system on cartilage.

【 授权许可】

CC BY-NC