Targeting intracellular Staphylococcus aureus to lower recurrence of orthopedic infection
Targeting intracellular Staphylococcus aureus to lower recurrence of orthopedic infection
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 10x 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.
intracellular bacteria, biofilm, osteoblast, orthopaedic infection, Staphylococcus aureus
1086-1092
Dusane, Devendra H.
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Kyrouac, Douglas
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Petersen, Iris
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Bushrow, Luke
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Calhoun, Jason H
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Phieffer, Laura S.
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Stoodley, Paul
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April 2018
Dusane, Devendra H.
9a47c5eb-5587-4f1d-bfd4-8548681be2bc
Kyrouac, Douglas
5e1ccc83-dfe1-49a8-b4cb-1da6baa516ed
Petersen, Iris
775efc20-f5e0-468e-be1b-7f4672463aca
Bushrow, Luke
6d1b64df-2af9-489b-bc39-3f20adad11f7
Calhoun, Jason H
893101a9-1c57-41b2-9f6b-619c7cf4caa6
Phieffer, Laura S.
28b90ba5-c210-4288-873a-0e834e93837d
Stoodley, Paul
08614665-92a9-4466-806e-20c6daeb483f
Dusane, Devendra H., Kyrouac, Douglas, Petersen, Iris, Bushrow, Luke, Calhoun, Jason H, Phieffer, Laura S. and Stoodley, Paul
(2018)
Targeting intracellular Staphylococcus aureus to lower recurrence of orthopedic infection.
Journal of Orthopaedic Research, 36 (4), .
(doi:10.1002/jor.23723).
Abstract
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 10x 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.
Text
Osteoblast manuscript JOR PSv2-Final Accept Changes
- Accepted Manuscript
More information
Accepted/In Press date: 8 September 2017
e-pub ahead of print date: 9 October 2017
Published date: April 2018
Keywords:
intracellular bacteria, biofilm, osteoblast, orthopaedic infection, Staphylococcus aureus
Identifiers
Local EPrints ID: 418522
URI: http://eprints.soton.ac.uk/id/eprint/418522
ISSN: 0736-0266
PURE UUID: fb456988-55d5-4928-8f3c-1ba56704f28a
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Date deposited: 09 Mar 2018 17:31
Last modified: 16 Mar 2024 06:17
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Contributors
Author:
Devendra H. Dusane
Author:
Douglas Kyrouac
Author:
Iris Petersen
Author:
Luke Bushrow
Author:
Jason H Calhoun
Author:
Laura S. Phieffer
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