Survival of Staphylococcus Epidermidis in Fibroblasts and Osteoblasts

is a leading cause of infections associated with indwelling medical devices, including prosthetic joint infection. While biofilm formation is assumed to be the main mechanism underlying the chronic infections causes, we hypothesized that also evades immune killing, contributing to its pathogenesis. Here, we show that prosthetic joint-associated isolates can persist intracellularly within human fibroblasts and inside human and mouse osteoblasts. We also show that the intracellularly persisting bacteria reside primarily within acidic phagolysosomes and that over the course of infection, small-colony variants are selected for. Moreover, upon eukaryotic cell death, these bacteria, which can outlive their host, can escape into the extracellular environment, providing them an opportunity to form biofilms on implant surfaces at delayed time points in implant-associated infection. In summary, the acidic phagolysosomes of fibroblasts and osteoblasts serve as reservoirs for chronic or delayed infection.