Targeting intracellular Staphylococcus aureus to lower recurrence of orthopaedic infection.

Autor: Dusane DH; Department of Microbial Infection and Immunity, The Ohio State University, 716 Biomedical Research Tower (BRT), 460 W 12th Ave, Columbus, 43210, Ohio., Kyrouac D; Department of Microbial Infection and Immunity, The Ohio State University, 716 Biomedical Research Tower (BRT), 460 W 12th Ave, Columbus, 43210, Ohio., Petersen I; Department of Microbial Infection and Immunity, The Ohio State University, 716 Biomedical Research Tower (BRT), 460 W 12th Ave, Columbus, 43210, Ohio., Bushrow L; Department of Microbial Infection and Immunity, The Ohio State University, 716 Biomedical Research Tower (BRT), 460 W 12th Ave, Columbus, 43210, Ohio., Calhoun JH; Department of Orthopaedics, The Ohio State University, Columbus, 43210, Ohio., Granger JF; Department of Orthopaedics, The Ohio State University, Columbus, 43210, Ohio., Phieffer LS; Department of Orthopaedics, The Ohio State University, Columbus, 43210, Ohio., Stoodley P; Department of Microbial Infection and Immunity, The Ohio State University, 716 Biomedical Research Tower (BRT), 460 W 12th Ave, Columbus, 43210, Ohio.; Department of Orthopaedics, The Ohio State University, Columbus, 43210, Ohio.; National Centre for Advanced Tribology at Southampton (nCATS), Mechanical Engineering, University of Southampton, Southampton, SO53 5BJ, UK.
Jazyk: angličtina
Zdroj: Journal of orthopaedic research : official publication of the Orthopaedic Research Society [J Orthop Res] 2018 Apr; Vol. 36 (4), pp. 1086-1092. Date of Electronic Publication: 2017 Oct 09.
DOI: 10.1002/jor.23723
Abstrakt: Staphylococcus aureus is often found in orthopaedic infections and may be protected from commonly prescribed antibiotics by forming biofilms or growing intracellularly within osteoblasts. To investigate the effect of non-antibiotic compounds in conjunction with antibiotics to clear intracellular and biofilm forming S. aureus causing osteomyelitis. SAOS-2 osteoblast-like cell lines were infected with S. aureus BB1279. Antibiotics (vancomycin, VAN; and dicloxacillin, DICLOX), bacterial efflux pump inhibitors (piperine, PIP; carbonyl cyanide m-chlorophenyl hydrazone, CCCP), and bone morphogenetic protein (BMP-2) were evaluated individually and in combination to kill intracellular bacteria. We present direct evidence that after gentamicin killed extracellular planktonic bacteria and antibiotics had been stopped, seeding from the infected osteoblasts grew as biofilms. VAN was ineffective in treating the intracellular bacteria even at 10× MIC; however in presence of PIP or CCCP the intracellular S. aureus was significantly reduced. Bacterial efflux pump inhibitors (PIP and CCCP) were effective in enhancing permeability of antibiotics within the osteoblasts and facilitated killing of intracellular S. aureus. Confocal laser scanning microscopy (CLSM) showed increased uptake of propidium iodide within osteoblasts in presence of PIP and CCCP. BMP-2 had no effect on growth of S. aureus either alone or in combination with antibiotics. Combined application of antibiotics and natural agents could help in the treatment of osteoblast infected intracellular bacteria and biofilms associated with osteomyelitis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1086-1092, 2018.
(© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)
Databáze: MEDLINE
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