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Antifungal, Cytotoxic, and Immunomodulatory Properties of Tea Tree Oil and Its Derivative Components: Potential Role in Management of Oral Candidosis in Cancer Patients

Candida albicans forms oral biofilms that cause disease and are difficult to treat with conventional antifungal agents. Tea tree oil (TTO) is a natural compound with reported antimicrobial and immunomodulatory activities. The aims of the study were to evaluate the antifungal efficacy of TTO and key...

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Autores principales: Ramage, Gordon, Milligan, Steven, Lappin, David F., Sherry, Leighann, Sweeney, Petrina, Williams, Craig, Bagg, Jeremy, Culshaw, Shauna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376416/
https://www.ncbi.nlm.nih.gov/pubmed/22719736
http://dx.doi.org/10.3389/fmicb.2012.00220
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author Ramage, Gordon
Milligan, Steven
Lappin, David F.
Sherry, Leighann
Sweeney, Petrina
Williams, Craig
Bagg, Jeremy
Culshaw, Shauna
author_facet Ramage, Gordon
Milligan, Steven
Lappin, David F.
Sherry, Leighann
Sweeney, Petrina
Williams, Craig
Bagg, Jeremy
Culshaw, Shauna
author_sort Ramage, Gordon
collection PubMed
description Candida albicans forms oral biofilms that cause disease and are difficult to treat with conventional antifungal agents. Tea tree oil (TTO) is a natural compound with reported antimicrobial and immunomodulatory activities. The aims of the study were to evaluate the antifungal efficacy of TTO and key derivatives against C. albicans biofilms, to assess the toxicological effects of TTO on a clinically relevant oral cell line, and to investigate its impact on inflammation. TTO and its derivatives were examined against 100 clinical strains of C. albicans. Planktonic minimum inhibitory concentrations (MICs) were determined using the CLSI M-27A broth microdilution method. Sessile MICs were determined using an XTT reduction assay. Inhibition, time-kill, and mode of action studies were performed. OKF6-TERT2 epithelial cells were used for cytotoxicity and cytokine expression assays. Planktonic C. albicans isolates were susceptible to TTO, terpinen-4-ol (T-4-ol), and α-terpineol, with an MIC(50) of 0.5, 0.25, and 0.25%, respectively. These three compounds also displayed potent activity against the 69 biofilm-forming strains, of which T-4-ol and α-terpineol displayed rapid kill kinetics. For all three compounds, 1 × MIC(50) effectively inhibited biofilm growth when C. albicans were treated at 0, 1, and 2 h post adhesion. By scanning electron microscopy analysis and PI uptake, TTO and derivative components were shown to be cell membrane active. TTO and T-4-ol were cytotoxic at 1 × MIC(50), whereas at 0.5 × MIC(50) T-4-ol displayed no significant toxicity. Transcript and protein analysis showed a reduction of IL-8 when treated with TTO and T-4-ol. These data provide further in vitro evidence that TTO and its derivative components, specifically T-4-ol, exhibit strong antimicrobial properties against fungal biofilms. T-4-ol has safety advantages over the complete essential oil and may be suitable for prophylaxis and treatment of established oropharyngeal candidosis. A clinical trial of T-4-ol is worthy of consideration.
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spelling pubmed-33764162012-06-20 Antifungal, Cytotoxic, and Immunomodulatory Properties of Tea Tree Oil and Its Derivative Components: Potential Role in Management of Oral Candidosis in Cancer Patients Ramage, Gordon Milligan, Steven Lappin, David F. Sherry, Leighann Sweeney, Petrina Williams, Craig Bagg, Jeremy Culshaw, Shauna Front Microbiol Microbiology Candida albicans forms oral biofilms that cause disease and are difficult to treat with conventional antifungal agents. Tea tree oil (TTO) is a natural compound with reported antimicrobial and immunomodulatory activities. The aims of the study were to evaluate the antifungal efficacy of TTO and key derivatives against C. albicans biofilms, to assess the toxicological effects of TTO on a clinically relevant oral cell line, and to investigate its impact on inflammation. TTO and its derivatives were examined against 100 clinical strains of C. albicans. Planktonic minimum inhibitory concentrations (MICs) were determined using the CLSI M-27A broth microdilution method. Sessile MICs were determined using an XTT reduction assay. Inhibition, time-kill, and mode of action studies were performed. OKF6-TERT2 epithelial cells were used for cytotoxicity and cytokine expression assays. Planktonic C. albicans isolates were susceptible to TTO, terpinen-4-ol (T-4-ol), and α-terpineol, with an MIC(50) of 0.5, 0.25, and 0.25%, respectively. These three compounds also displayed potent activity against the 69 biofilm-forming strains, of which T-4-ol and α-terpineol displayed rapid kill kinetics. For all three compounds, 1 × MIC(50) effectively inhibited biofilm growth when C. albicans were treated at 0, 1, and 2 h post adhesion. By scanning electron microscopy analysis and PI uptake, TTO and derivative components were shown to be cell membrane active. TTO and T-4-ol were cytotoxic at 1 × MIC(50), whereas at 0.5 × MIC(50) T-4-ol displayed no significant toxicity. Transcript and protein analysis showed a reduction of IL-8 when treated with TTO and T-4-ol. These data provide further in vitro evidence that TTO and its derivative components, specifically T-4-ol, exhibit strong antimicrobial properties against fungal biofilms. T-4-ol has safety advantages over the complete essential oil and may be suitable for prophylaxis and treatment of established oropharyngeal candidosis. A clinical trial of T-4-ol is worthy of consideration. Frontiers Research Foundation 2012-06-18 /pmc/articles/PMC3376416/ /pubmed/22719736 http://dx.doi.org/10.3389/fmicb.2012.00220 Text en Copyright © 2012 Ramage, Milligan, Lappin, Sherry, Sweeney, Williams, Bagg and Culshaw. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Microbiology
Ramage, Gordon
Milligan, Steven
Lappin, David F.
Sherry, Leighann
Sweeney, Petrina
Williams, Craig
Bagg, Jeremy
Culshaw, Shauna
Antifungal, Cytotoxic, and Immunomodulatory Properties of Tea Tree Oil and Its Derivative Components: Potential Role in Management of Oral Candidosis in Cancer Patients
title Antifungal, Cytotoxic, and Immunomodulatory Properties of Tea Tree Oil and Its Derivative Components: Potential Role in Management of Oral Candidosis in Cancer Patients
title_full Antifungal, Cytotoxic, and Immunomodulatory Properties of Tea Tree Oil and Its Derivative Components: Potential Role in Management of Oral Candidosis in Cancer Patients
title_fullStr Antifungal, Cytotoxic, and Immunomodulatory Properties of Tea Tree Oil and Its Derivative Components: Potential Role in Management of Oral Candidosis in Cancer Patients
title_full_unstemmed Antifungal, Cytotoxic, and Immunomodulatory Properties of Tea Tree Oil and Its Derivative Components: Potential Role in Management of Oral Candidosis in Cancer Patients
title_short Antifungal, Cytotoxic, and Immunomodulatory Properties of Tea Tree Oil and Its Derivative Components: Potential Role in Management of Oral Candidosis in Cancer Patients
title_sort antifungal, cytotoxic, and immunomodulatory properties of tea tree oil and its derivative components: potential role in management of oral candidosis in cancer patients
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376416/
https://www.ncbi.nlm.nih.gov/pubmed/22719736
http://dx.doi.org/10.3389/fmicb.2012.00220
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