The University of Southampton
University of Southampton Institutional Repository

Targeting intracellular Staphylococcus aureus to lower recurrence of orthopedic infection

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
0736-0266
1086-1092
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.
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), 1086-1092. (doi:10.1002/jor.23723).

Record type: Article

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
Download (9MB)

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
ORCID for Paul Stoodley: ORCID iD orcid.org/0000-0001-6069-273X

Catalogue record

Date deposited: 09 Mar 2018 17:31
Last modified: 16 Mar 2024 06:17

Export record

Altmetrics

Contributors

Author: Devendra H. Dusane
Author: Douglas Kyrouac
Author: Iris Petersen
Author: Luke Bushrow
Author: Jason H Calhoun
Author: Laura S. Phieffer
Author: Paul Stoodley ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×