5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a novel treatment for intravascular catheter infections due to Staphylococcus aureus
Objectives: Biofilm infections of intravascular catheters caused by Staphylococcus aureus may be treated with catheter lock solutions (CLSs). Here we investigated the antibacterial activity, cytotoxicity and CLS potential of 5-hydroxyethyl-3-tetradecanoyltetramic acid (5HE-C14-TMA) compared with the...
| Main Authors: | , , , , , , , |
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| Format: | Article |
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Oxford University Press
2016
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| Online Access: | https://eprints.nottingham.ac.uk/39576/ |
| _version_ | 1848795868572942336 |
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| author | Zapotoczna, Marta Murray, Ewan J. Hogan, Siobhan O'Gara, James P. Chhabra, Siri Ram Chan, Weng C. O'Neill, Eoghan Williams, Paul |
| author_facet | Zapotoczna, Marta Murray, Ewan J. Hogan, Siobhan O'Gara, James P. Chhabra, Siri Ram Chan, Weng C. O'Neill, Eoghan Williams, Paul |
| author_sort | Zapotoczna, Marta |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Objectives: Biofilm infections of intravascular catheters caused by Staphylococcus aureus may be treated with catheter lock solutions (CLSs). Here we investigated the antibacterial activity, cytotoxicity and CLS potential of 5-hydroxyethyl-3-tetradecanoyltetramic acid (5HE-C14-TMA) compared with the related compounds 3-tetradecanoyltetronic (C14-TOA) and 3-tetradecanoylthiotetronic (C14-TTA), which are variants of quorum sensing signalling molecules produced by Pseudomonas aeruginosa.
Methods: Antibacterial activity and mechanism of action of 5HE-C14-TMA, C14-TOA and C14-TTA were determined via MIC, bacterial killing, membrane potential and permeability assays. Susceptibility of S. aureus biofilms formed in the presence of plasma in vitro was investigated, MTT cytotoxicity testing was undertaken and cytokine release in human blood upon exposure to 5HE-C14-TMA and/or S. aureus biofilms was quantified. The effectiveness of 5HE-C14-TMA as CLS therapy in vivo was assessed using a rat intravascular catheter biofilm infection model.
Results: MICs of 5HE-C14-TMA, C14-TOA and C14-TTA ranged from 2 to 4 mg/L. 5HE-C14-TMA and C14-TTA were bactericidal; all three compounds perturbed the staphylococcal membrane by increasing membrane permeability, depolarized the transmembrane potential and caused ATP leakage. Cytotoxicity and haemolytic activity were compound and target cell type-dependent. 5HE-C14-TMA reduced S. aureus biofilm viability in a dose-dependent manner in vitro and in vivo and did not trigger release of cytokines in human blood, but inhibited the high levels of IL-8 and TNF-α induced by S. aureus biofilms.
Conclusions: 5HE-C14-TMA, C14-TOA and C14-TTA are membrane-active agents. 5HE-C14-TMA was the most potent, eradicating S. aureus biofilms at 512–1024 mg/L both in vitro and in vivo as a CLS. |
| first_indexed | 2025-11-14T19:38:56Z |
| format | Article |
| id | nottingham-39576 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:38:56Z |
| publishDate | 2016 |
| publisher | Oxford University Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-395762020-05-04T18:25:09Z https://eprints.nottingham.ac.uk/39576/ 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a novel treatment for intravascular catheter infections due to Staphylococcus aureus Zapotoczna, Marta Murray, Ewan J. Hogan, Siobhan O'Gara, James P. Chhabra, Siri Ram Chan, Weng C. O'Neill, Eoghan Williams, Paul Objectives: Biofilm infections of intravascular catheters caused by Staphylococcus aureus may be treated with catheter lock solutions (CLSs). Here we investigated the antibacterial activity, cytotoxicity and CLS potential of 5-hydroxyethyl-3-tetradecanoyltetramic acid (5HE-C14-TMA) compared with the related compounds 3-tetradecanoyltetronic (C14-TOA) and 3-tetradecanoylthiotetronic (C14-TTA), which are variants of quorum sensing signalling molecules produced by Pseudomonas aeruginosa. Methods: Antibacterial activity and mechanism of action of 5HE-C14-TMA, C14-TOA and C14-TTA were determined via MIC, bacterial killing, membrane potential and permeability assays. Susceptibility of S. aureus biofilms formed in the presence of plasma in vitro was investigated, MTT cytotoxicity testing was undertaken and cytokine release in human blood upon exposure to 5HE-C14-TMA and/or S. aureus biofilms was quantified. The effectiveness of 5HE-C14-TMA as CLS therapy in vivo was assessed using a rat intravascular catheter biofilm infection model. Results: MICs of 5HE-C14-TMA, C14-TOA and C14-TTA ranged from 2 to 4 mg/L. 5HE-C14-TMA and C14-TTA were bactericidal; all three compounds perturbed the staphylococcal membrane by increasing membrane permeability, depolarized the transmembrane potential and caused ATP leakage. Cytotoxicity and haemolytic activity were compound and target cell type-dependent. 5HE-C14-TMA reduced S. aureus biofilm viability in a dose-dependent manner in vitro and in vivo and did not trigger release of cytokines in human blood, but inhibited the high levels of IL-8 and TNF-α induced by S. aureus biofilms. Conclusions: 5HE-C14-TMA, C14-TOA and C14-TTA are membrane-active agents. 5HE-C14-TMA was the most potent, eradicating S. aureus biofilms at 512–1024 mg/L both in vitro and in vivo as a CLS. Oxford University Press 2016-12-20 Article PeerReviewed Zapotoczna, Marta, Murray, Ewan J., Hogan, Siobhan, O'Gara, James P., Chhabra, Siri Ram, Chan, Weng C., O'Neill, Eoghan and Williams, Paul (2016) 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a novel treatment for intravascular catheter infections due to Staphylococcus aureus. Journal of Antimicrobial Chemotherapy . ISSN 1460-2091 http://jac.oxfordjournals.org/content/early/2016/12/02/jac.dkw482 doi:10.1093/jac/dkw482 doi:10.1093/jac/dkw482 |
| spellingShingle | Zapotoczna, Marta Murray, Ewan J. Hogan, Siobhan O'Gara, James P. Chhabra, Siri Ram Chan, Weng C. O'Neill, Eoghan Williams, Paul 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a novel treatment for intravascular catheter infections due to Staphylococcus aureus |
| title | 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a
novel treatment for intravascular catheter infections due to Staphylococcus aureus |
| title_full | 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a
novel treatment for intravascular catheter infections due to Staphylococcus aureus |
| title_fullStr | 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a
novel treatment for intravascular catheter infections due to Staphylococcus aureus |
| title_full_unstemmed | 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a
novel treatment for intravascular catheter infections due to Staphylococcus aureus |
| title_short | 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a
novel treatment for intravascular catheter infections due to Staphylococcus aureus |
| title_sort | 5-hydroxyethyl-3-tetradecanoyltetramic acid represents a
novel treatment for intravascular catheter infections due to staphylococcus aureus |
| url | https://eprints.nottingham.ac.uk/39576/ https://eprints.nottingham.ac.uk/39576/ https://eprints.nottingham.ac.uk/39576/ |