title: Orthopedic implant infections: Incompetence of Staphylococcus epidermidis, Staphylococcus lugdunensis, and Enterococcus faecalis to invade osteoblasts.
abstract: Septic failure is still the major complication of prosthetic implants. Entering host cells, bacteria hide from host immune defenses, shelter from extracellular antibiotics, and cause chronic infection. Staphylococcus aureus, the leading etiologic agent of orthopedic implant infections, is able to enter bone cells and induce osteoblast apoptosis, osteoclast recruitment, and highly destructive osteomyelitis. Staphylococcus epidermidis, Staphylococcus lugdunensis, and Enterococcus faecalis are opportunistic pathogens causative of implant-related infections. This study investigated the ability to internalize into osteoblastic MG63 cells of 22 S. epidermidis, 9 S. lugdunensis, and 21 E. faecalis clinical isolates from orthopedic implant infections. Isolates were categorized in clusters by ribotyping. Internalization assay was carried out by means of a microtiter plate-based method. S. epidermidis, S. lugdunensis, and E. faecalis strains turned out incompetent to enter osteoblasts, exhibiting negligible internalization into MG63 cells, nearly three orders of magnitude lower than that of S. aureus. Osteoblast invasion does not appear as a pathogenetic mechanism utilized by S. epidermidis, S. lugdunensis, or E. faecalis for infecting orthopedic implants. Moreover, it can be inferred that intracellularly active antimicrobials should not be necessary against implant infections caused by the three bacterial species. Finally, implications with the uptake of biomaterial microparticles by nonphagocytic cells are enlightened. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 788-801, 2016.
authors.affiliation: Research Unit on Implant Infections, Rizzoli Orthopedic Institute, Bologna, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Campoccia
authors.affiliation: Research Unit on Implant Infections, Rizzoli Orthopedic Institute, Bologna, Italy.|Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Testoni
authors.affiliation: Research Unit on Implant Infections, Rizzoli Orthopedic Institute, Bologna, Italy.|Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ravaioli
authors.affiliation: Research Unit on Implant Infections, Rizzoli Orthopedic Institute, Bologna, Italy.|Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cangini
authors.affiliation: Microbiology Analysis Section of the Musculoskeletal Tissue Bank, Rizzoli Orthopedic Institute, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Maso
authors.affiliation: Department of Molecular Medicine, Unit of Biochemistry, University of Pavia, Pavia, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Speziale
authors.affiliation: Research Unit on Implant Infections, Rizzoli Orthopedic Institute, Bologna, Italy.|Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Montanaro
authors.affiliation: Department of Molecular Medicine, Center for Tissue Engineering (CIT), INSTM UdR of Pavia, University of Pavia, Pavia, Italy.|Department of Occupational Medicine, Ergonomy and Disability, Nanotechnology Laboratory, Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Visai
authors.affiliation: Research Unit on Implant Infections, Rizzoli Orthopedic Institute, Bologna, Italy.|Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Carla Renata
authors.initials: CR
authors.lastname: Arciola
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D045744:Cell Line, Tumor; D015169:Colony Count, Microbial; D013293:Enterococcus faecalis / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000382:microbiology*; D019736:Prostheses and Implants / Q000382:microbiology*; D016459:Prosthesis-Related Infections / Q000382:microbiology* / Q000473:pathology*; D021521:Ribotyping; D013212:Staphylococcus epidermidis / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D057787:Staphylococcus lugdunensis / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*
chemical_list: D000617:Aminoglycosides
keywords: Enterococcus faecalis; MG63 cells; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus lugdunensis; bone; implant infections; internalization; molecular epidemiology; osteoblasts; osteomyelitis; ribotyping