Serratiopeptidase reduces the invasion of osteoblasts by Staphylococcus aureus

Abstract

Finding new strategies to counteract periprosthetic infection and implant failure is a main target in orthopedics. Staphylococcus aureus, the leading etiologic agent of orthopedic implant infections, is able to enter and kill osteoblasts, to stimulate pro-inflammatory chemokine secretion, to recruit osteoclasts, and to cause inflammatory osteolysis. Moreover, by entering eukaryotic cells, staphylococci hide from the host immune defenses and shelter from the extracellular antibiotics. Thus, infection persists, inflammation thrives, and a highly destructive osteomyelitis occurs around the implant. The ability of serratiopeptidase (SPEP), a metalloprotease by Serratia marcescens, to control S. aureus invasion of osteoblastic MG-63 cells and pro-inflammatory chemokine MCP-1 secretion was evaluated. Human osteoblast cells were infected with staphylococcal strains in the presence and in the absence of SPEP. Cell proliferation and cell viability were also evaluated. The release of pro-inflammatory chemokine MCP-1 was evaluated after the exposure of the osteoblast cells to staphylococcal strains. The significance of the differences in the results of each test and the relative control values was determined with Student’s t-test. SPEP impairs their invasiveness into osteoblasts, without affecting the viability and proliferation of bone cells, and tones down their production of MCP-1. We recognize SPEP as a potential tool against S. aureus bone infection and destruction.

Different Modulatory Effects of Four Methicillin‐Resistant <em>Staphylococcus aureus</em> Clones on MG-63 Osteoblast-Like Cells

“…In order to shed more light on the different behavior observed in these strains, we also determined their influence on the gene expression of IL-6, TNF-α, TGF-β1, and GAPDH as well as Nrf2 and its downstream effector heme oxygenase 1 (HO-1). The human MG-63 osteoblast-like cell line was selected not only because it represents a validated model to study the pro-inflammatory response to bacterial infection [27][28][29], but also because shows a number of features typical of an undifferentiated osteoblast phenotype including the synthesis of collagen types I and III, a low basal expression of alkaline phosphatase which is increased following 1,25-dihydroxyvitamin D (1,25(OH)2D) administration, and the production of osteocalcin in the presence of 1,25(OH)2D [30][31][32].…”

Serratiopeptidase: Insights into the therapeutic applications

“…Serratiopeptidase is a natural molecule that is being used for decades, hence commonly considered as safe. The safety of this enzyme in different areas of therapeutics is supported by several studies [ 15 , 19 , 22 , 48 , 54 , 72 ] in which no side effects or adverse events were reported. However, some studies have reported adverse effects of this molecule, but at a rare frequency.…”

“…Further, authors suggested the need for research to identify the mechanism of action of serratiopeptidase in biofilm regulation that is unrelated to proteolytic activity. Recently, [ 54 ] evaluated the anti-biofilm ability of serratiopeptidase against Staphalococcus aureus infection on osteoblastic MG-63 cells. The pro-inflammatory chemokine MCP-1 was used as an immunological marker.…”

Necrotizing Soft Tissue Infections Staphylococcus aureus - but not Streptococcus pyogenes-isolates display high rate of internalization and cytotoxicity toward human myoblasts

“…the level of SA internalization is ca. 17% in human embryonic kidney cells (12), 8% in endothelial cells (12), 2% in human alveolar epithelial cells (A549) (K. Moreau, unpublished data), <1% HELA epithelial cells (13), <1% within osteoblast (14) and <2% in osteoclast (15). We could demonstrate that this high rate of internalization depends on several of the known pathways of S. aureus internalization with a preeminence of the FnBP-Fibronectin-α5β1 integrin-mediated pathway.…”