Ooi, N, Eady, EA, Cove, JH et al. (1 more author) (2015) Redox-active compounds with a history of human use: antistaphylococcal action and potential for repurposing as topical antibiofilm agents. Journal of Antimicrobial Chemotherapy, 70 (2). 479 - 488. ISSN 0305-7453
Abstract
Objectives: To investigate the antistaphylococcal/antibiofilm activity and mode of action (MOA) of a panel of redox-active (RA) compounds with a history of human use and to provide a preliminary preclinical assessment of their potential for topical treatment of staphylococcal infections, including those involving a biofilm component. Methods: Antistaphylococcal activity was evaluated by broth microdilution and by time-kill studies with growing and slow- or non-growing cells. The antibiofilm activity of RA compounds, alone and in combination with established antibacterial agents, was assessed using the Calgary Biofilm Device. Established assays were used to examine the membrane-perturbing effects of RA compounds, to measure penetration into biofilms and physical disruption of biofilms and to assess resistance potential. A living skin equivalent model was used to assess the effects of RA compounds on human skin. Results: All 15 RA compounds tested displayed antistaphylococcal activity against planktonic cultures (MIC 0.25-128 mg/L) and 7 eradicated staphylococcal biofilms (minimum biofilm eradication concentration 4-256 mg/L). The MOA of all compounds involved perturbation of the bacterial membrane, whilst selected compounds with antibiofilm activity caused destructuring of the biofilm matrix. The two most promising agents [celastrol and nordihydroguaiaretic acid (NDGA)] in respect of antibacterial potency and selective toxicity against bacterial membranes acted synergistically with gentamicin against biofilms, did not damage artificial skin following topical application and exhibited low resistance potential. Conclusions: In contrast to established antibacterial drugs, some RA compounds are capable of eradicating staphylococcal biofilms. Of these, celastrol and NDGA represent particularly attractive candidates for development as topical antistaphylococcal biofilm treatments.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Antibacterial; Biofilm; Mode of action; Staphylococcus aureus; Staphylococcus epidermidis |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 25 Mar 2015 09:57 |
Last Modified: | 15 Oct 2019 15:41 |
Published Version: | http://dx.doi.org/10.1093/jac/dku409 |
Status: | Published |
Publisher: | Oxford University Press (OUP) |
Identification Number: | 10.1093/jac/dku409 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:83655 |