The role of Staphylococcus aureus small colony variants in intraosseous invasion and colonization in periprosthetic joint infection

Yuanqing Cai; Changyu Huang; Xiaoqing Chen; Yang Chen; Zida Huang; Chaofan Zhang; Wenming Zhang; Xinyu Fang

doi:10.1302/2046-3758.1112.BJR-2021-0590.R1

The role of Staphylococcus aureus small colony variants in intraosseous invasion and colonization in periprosthetic joint infection

Bone Joint Res. 2022 Dec;11(12):843-853. doi: 10.1302/2046-3758.1112.BJR-2021-0590.R1.

Authors

Yuanqing Cai^{1

2

3}, Changyu Huang^{1

3}, Xiaoqing Chen⁴, Yang Chen^{1

3}, Zida Huang^{1

3}, Chaofan Zhang^{1

3}, Wenming Zhang^{1

3}, Xinyu Fang^{1

3}

Affiliations

¹ Department of Orthopaedics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
² Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
³ Department of Orthopedic Surgery, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
⁴ Department of Orthopaedics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China.

PMID: 36453022
PMCID: PMC9792874
DOI: 10.1302/2046-3758.1112.BJR-2021-0590.R1

Abstract

Aims: This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI).

Methods: A PJI diagnosis was made according to the MusculoSkeletal Infection Society (MSIS) for PJI. Bone and tissue samples were collected intraoperatively and the intracellular invasion and intraosseous colonization were detected. Transcriptomics of PJI samples were analyzed and verified by polymerase chain reaction (PCR).

Results: SCVs can be isolated from samples collected from chronic PJIs intraoperatively. Transmission electron microscopy (TEM) and immunofluorescence (IF) showed that there was more S. aureus in bone samples collected from chronic PJIs, but much less in bone samples from acute PJIs, providing a potential mechanism of PJI. Immunofluorescence results showed that SCVs of S. aureus were more likely to invade osteoblasts in vitro. Furthermore, TEM and IF also demonstrated that SCVs of S. aureus were more likely to invade and colonize in vivo. Cluster analysis and principal component analysis (PCA) showed that there were substantial differences in gene expression profiles between chronic and acute PJI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these differentially expressed genes were enriched to chemokine-related signal pathways. PCR also verified these results.

Conclusion: Our study has shown that the S. aureus SCVs have a greater ability to invade and colonize in bone, resulting in S. aureus remaining in bone tissues long-term, thus explaining the pathogenesis of chronic PJI.Cite this article: Bone Joint Res 2022;11(12):843-853.

Keywords: Bone and tissue; Periprosthetic joint infection; Periprosthetic joint infection (PJI); Small colony variant; Staphylococcus aureus; chemokines; electron microscopy; gene expression profiles; intraosseous; musculoskeletal infections; osteoblasts; pathogenesis.