Novel Insights into Staphylococcus aureus Deep Bone Infections: the Involvement of Osteocytes

• Published in: mBio 2018-04, Vol.9 (2)
• Main Authors: Yang, Dongqing, Wijenayaka, Asiri R, Solomon, Lucian B, Pederson, Stephen M, Findlay, David M, Kidd, Stephen P, Atkins, Gerald J
• Format: Article
• Language: English
• Subjects: bone infection; Cells, Cultured; Humans; Models, Biological; Observation; Osteoarthritis - physiopathology; Osteocytes - microbiology; osteomyelitis; periprosthetic joint infection; Prosthesis-Related Infections - physiopathology; small-colony variant; Staphylococcal Infections - physiopathology; Staphylococcus aureus; Staphylococcus aureus - pathogenicity; stress adaptation
• ISSN: 2161-2129; 2150-7511
• DOI: 10.1128/mBio.00415-18

Periprosthetic joint infection (PJI) is a potentially devastating complication of orthopedic joint replacement surgery. PJI with associated osteomyelitis is particularly problematic and difficult to cure. Whether viable osteocytes, the predominant cell type in mineralized bone tissue, have a role in these infections is not clear, although their involvement might contribute to the difficulty in detecting and clearing PJI. Here, using , the most common pathogen in PJI, we demonstrate intracellular infection of human-osteocyte-like cells and adaptation by forming quasi-dormant small-colony variants (SCVs). Consistent patterns of host gene expression were observed between -infected osteocyte-like cultures, an human bone infection model, and bone samples obtained from PJI patients. Finally, we confirm infection of osteocytes in clinical cases of PJI. Our findings are consistent with osteocyte infection being a feature of human PJI and suggest that this cell type may provide a reservoir for silent or persistent infection. We suggest that elucidating the molecular/cellular mechanism(s) of osteocyte-bacterium interactions will contribute to better understanding of PJI and osteomyelitis, improved pathogen detection, and treatment. Periprosthetic joint infections (PJIs) are increasing and are recognized as one of the most common modes of failure of joint replacements. Osteomyelitis arising from PJI is challenging to treat and difficult to cure and increases patient mortality 5-fold. is the most common pathogen causing PJI. PJI can have subtle symptoms and lie dormant or go undiagnosed for many years, suggesting persistent bacterial infection. Osteocytes, the major bone cell type, reside in bony caves and tunnels, the lacuno-canalicular system. We report here that can infect and reside in human osteocytes without causing cell death both experimentally and in bone samples from patients with PJI. We demonstrate that osteocytes respond to infection by the differential regulation of a large number of genes. adapts during intracellular infection of osteocytes by adopting the quasi-dormant small-colony variant (SCV) lifestyle, which might contribute to persistent or silent infection. Our findings shed new light on the etiology of PJI and osteomyelitis in general.