Effect of endolysin XZ.700 on monocyte differentiation into osteoclasts and foreign body giant cells

Periprosthetic joint infections due to biofilm formation are a major concern in orthopaedic and dental implant surgery. Current treatment options use antibiotics, but antibiotic-resistant bacteria in the biofilm cause treatment failure. Bacteriophage-derived endolysin XZ.700 is highly promising to fight anti-microbial resistance, since it exhibits potent anti-biofilm activity and low cell toxicity. However, whether it affects immunomodulatory cell formation is currently unknown. Therefore, this study aimed to determine whether endolysin XZ.700 affects monocyte differentiation into osteoclasts and/or foreign body giant cells in vitro. Formation of multinucleated osteoclasts and foreign body giant cells from CD14⁺ monocytes cultured without/with endolysin XZ.700 (25, 50, 75 μg/ml) was assessed after 7, 14, and 21 days, as well as differentiation, multinucleation, and cell activation-related gene expression. Endolysin XZ.700 decreased formation of osteoclasts with 3-5 nuclei/cell, but increased those with >10 nuclei/cell after 21 days, resulting in overall inhibition of total osteoclast formation. The formation of foreign body giant cells with 3-5 nuclei/cell, but not 6-10 or >10 nuclei/cell, was significantly decreased by endolysin XZ.700 at all time points. Only 25 μg/ml endolysin XZ.700 decreased total foreign body giant cell formation after 21 days. Endolysin XZ.700 downregulated differentiation-related gene expression, but upregulated cytokine-related gene expression in monocytes differentiating into osteoclasts or foreign body giant cells. In conclusion, the biofilm-reducing agent endolysin XZ.700 decreases the formation of immunomodulatory cells, i.e. foreign body giant cells and osteoclasts, indicating that it might be highly promising as a novel antimicrobial, with short term administration as the safest mode of treatment.