Septic arthritis in an in vivo murine model induced by Staphylococcus aureus <subtitle>a comparison between actions of the haemolysin toxin and the effects of the host immune response</subtitle>
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 viabili...
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| Format: | Article |
| Language: | English |
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The British Editorial Society of Bone & Joint Surgery
2022-09-01
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| Series: | Bone & Joint Research |
| Subjects: | |
| Online Access: | https://online.boneandjoint.org.uk/doi/10.1302/2046-3758.119.BJR-2022-0016.R1 |
| _version_ | 1811258260623196160 |
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| author | Rhys G. E. Clement Andrew C. Hall Seng J. Wong Sarah E. M. Howie A. Hamish R. W. Simpson |
| author_facet | Rhys G. E. Clement Andrew C. Hall Seng J. Wong Sarah E. M. Howie A. Hamish R. W. Simpson |
| author_sort | Rhys G. E. Clement |
| collection | DOAJ |
| description | 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.Cite this article: Bone Joint Res 2022;11(9):669–678. |
| first_indexed | 2024-04-12T18:10:34Z |
| format | Article |
| id | doaj.art-e2c62e914b36443dac04c19664585447 |
| institution | Directory Open Access Journal |
| issn | 2046-3758 |
| language | English |
| last_indexed | 2024-04-12T18:10:34Z |
| publishDate | 2022-09-01 |
| publisher | The British Editorial Society of Bone & Joint Surgery |
| record_format | Article |
| series | Bone & Joint Research |
| spelling | doaj.art-e2c62e914b36443dac04c196645854472022-12-22T03:21:50ZengThe British Editorial Society of Bone & Joint SurgeryBone & Joint Research2046-37582022-09-0111966967810.1302/2046-3758.119.BJR-2022-0016.R1Septic arthritis in an in vivo murine model induced by Staphylococcus aureus <subtitle>a comparison between actions of the haemolysin toxin and the effects of the host immune response</subtitle>Rhys G. E. Clement0Andrew C. Hall1Seng J. Wong2Sarah E. M. Howie3A. Hamish R. W. Simpson4Department of Orthopaedics and Trauma, University of Edinburgh, Edinburgh, UKDeanery of Biomedical Sciences, The University of Edinburgh, Edinburgh, UKDepartment of Orthopaedic Surgery, Singapore General Hospital, Singapore, SingaporeMRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UKDepartment of Orthopaedics and Trauma, University of Edinburgh, Edinburgh, UKAimsStaphylococcus 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.Cite this article: Bone Joint Res 2022;11(9):669–678.https://online.boneandjoint.org.uk/doi/10.1302/2046-3758.119.BJR-2022-0016.R1Septic arthritisHla toxinCartilageChondrocyteStaphylococcus aureusseptic arthritis |
| spellingShingle | Rhys G. E. Clement Andrew C. Hall Seng J. Wong Sarah E. M. Howie A. Hamish R. W. Simpson Septic arthritis in an in vivo murine model induced by Staphylococcus aureus <subtitle>a comparison between actions of the haemolysin toxin and the effects of the host immune response</subtitle> Bone & Joint Research Septic arthritis Hla toxin Cartilage Chondrocyte Staphylococcus aureus septic arthritis |
| title | Septic arthritis in an in vivo murine model induced by Staphylococcus aureus <subtitle>a comparison between actions of the haemolysin toxin and the effects of the host immune response</subtitle> |
| title_full | Septic arthritis in an in vivo murine model induced by Staphylococcus aureus <subtitle>a comparison between actions of the haemolysin toxin and the effects of the host immune response</subtitle> |
| title_fullStr | Septic arthritis in an in vivo murine model induced by Staphylococcus aureus <subtitle>a comparison between actions of the haemolysin toxin and the effects of the host immune response</subtitle> |
| title_full_unstemmed | Septic arthritis in an in vivo murine model induced by Staphylococcus aureus <subtitle>a comparison between actions of the haemolysin toxin and the effects of the host immune response</subtitle> |
| title_short | Septic arthritis in an in vivo murine model induced by Staphylococcus aureus <subtitle>a comparison between actions of the haemolysin toxin and the effects of the host immune response</subtitle> |
| title_sort | septic arthritis in an in vivo murine model induced by staphylococcus aureus subtitle a comparison between actions of the haemolysin toxin and the effects of the host immune response subtitle |
| topic | Septic arthritis Hla toxin Cartilage Chondrocyte Staphylococcus aureus septic arthritis |
| url | https://online.boneandjoint.org.uk/doi/10.1302/2046-3758.119.BJR-2022-0016.R1 |
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