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A Human Osteocyte Cell Line Model for Studying Staphylococcus aureus Persistence in Osteomyelitis
Nicholas J Gunn1, Anja R Zelmer1, Stephen P Kidd2,3
1Centre for Orthopaedic & Trauma Research, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.
Frontiers in Cellular and Infection Microbiology
|November 22, 2021
Summary
A novel cell model using osteocyte-like cells (SaOS2-OY) effectively mimics intracellular Staphylococcus aureus infections, revealing bacterial persistence and host immune responses relevant to osteomyelitis treatment.
Area of Science:
- Biomedical research
- Infectious diseases
- Cell biology
Background:
- Periprosthetic joint infections and osteomyelitis caused by Staphylococcus aureus are difficult to treat, often recurring.
- Intracellular bacterial infections within host cells, particularly osteocytes, are implicated in treatment failure but are understudied.
- Osteocytes form a bone-wide syncytium, potentially facilitating bacterial spread and evading immune detection.
Purpose of the Study:
- To evaluate the human osteosarcoma cell line SaOS2, differentiated into an osteocyte-like stage (SaOS2-OY), as an in vitro model for intracellular Staphylococcus aureus infection.
- To investigate host-pathogen interactions within this model, focusing on bacterial persistence and host cell responses.
- To assess the suitability of the SaOS2-OY model for predicting in vivo interactions and testing antimicrobial strategies.
Main Methods:
- Differentiated SaOS2 cells (SaOS2-OY) and undifferentiated SaOS2 cells (SaOS2-OB) were infected with Staphylococcus aureus.
- Intracellular bacterial survival and growth phenotypes were monitored over a 15-day period.
- Changes in the expression of immunomodulatory mediators in infected SaOS2-OY cells were analyzed.
Main Results:
- Staphylococcus aureus established stable intracellular infections in SaOS2-OY cells, but not in SaOS2-OB cells.
- In SaOS2-OY cells, S. aureus adopted a quasi-dormant small colony variant (SCV) phenotype.
- Infected SaOS2-OY cells showed altered expression of immunomodulatory mediators, mirroring primary osteocyte responses.
Conclusions:
- The SaOS2-OY cell line serves as a suitable and predictive in vitro model for studying intracellular Staphylococcus aureus infections in osteocytes.
- This model can elucidate mechanisms of bacterial persistence within bone.
- The SaOS2-OY model offers a platform for evaluating novel antimicrobial therapies against persistent bone infections.
