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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.

Ramage G, Milligan S, Lappin DF, Sherry L, Sweeney P, Williams C, Bagg J, Culshaw S - Front Microbiol (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, UK.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Candida albicans biofilm development is inhibited by TTO, T-4-ol, and α-terpineol. Standardized C. albicans (1 × 106 cells/ml) were added to a flat-bottomed 96-well plate and treated with (A) 0.5 and (B) 1 × SMIC50 for 0, 1, 2, and 4 h post incubation. Biofilms were subsequently allowed to develop for 24 h. Resultant biofilms were quantified using a crystal violet assay read at 570 nm in a microtiter plate reader (FluoStar Omega, BMG Labtech). Four isolates were used for each assay, and this was performed on two independent occasions in triplicate. *p < 0.05. Error bars represent the ±standard error of the mean.
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Figure 2: Candida albicans biofilm development is inhibited by TTO, T-4-ol, and α-terpineol. Standardized C. albicans (1 × 106 cells/ml) were added to a flat-bottomed 96-well plate and treated with (A) 0.5 and (B) 1 × SMIC50 for 0, 1, 2, and 4 h post incubation. Biofilms were subsequently allowed to develop for 24 h. Resultant biofilms were quantified using a crystal violet assay read at 570 nm in a microtiter plate reader (FluoStar Omega, BMG Labtech). Four isolates were used for each assay, and this was performed on two independent occasions in triplicate. *p < 0.05. Error bars represent the ±standard error of the mean.

Mentions: Inhibition of biofilm formation was assessed for these three compounds at 0.5 and 1 × MIC50 by assessing biofilm biomass. It was shown for all compounds that 1 × MIC50 was able to inhibit biofilm growth effectively when treated at 0, 1, and 2 h post adhesion (8.5−12% biomass compared to control). At 4 h post adhesion, by which time cells had began to form hyphae, treatment with TTO, T-4-ol, and α-terpineol further suppressed biofilm proliferation by 71, 74, and 82% that of the control (Figure 2A). No significant differences were observed between the treatments at each time point. Treatment with 0.5 × MIC50 was overall less effective at inhibiting biofilm growth most notably with TTO, which displayed a time dependent reduction in inhibition, showing a 44% inhibition of cells treated at 4 h (Figure 2B). Both T-4-ol and α-terpineol were significantly more effective against 1 and 2 h cells (p < 0.05), inhibiting biofilm formation by >80%. However, this inhibition was reduced against the 4 h cells (54 and 58%, respectively).


Antifungal, cytotoxic, and immunomodulatory properties of tea tree oil and its derivative components: potential role in management of oral candidosis in cancer patients.

Ramage G, Milligan S, Lappin DF, Sherry L, Sweeney P, Williams C, Bagg J, Culshaw S - Front Microbiol (2012)

Candida albicans biofilm development is inhibited by TTO, T-4-ol, and α-terpineol. Standardized C. albicans (1 × 106 cells/ml) were added to a flat-bottomed 96-well plate and treated with (A) 0.5 and (B) 1 × SMIC50 for 0, 1, 2, and 4 h post incubation. Biofilms were subsequently allowed to develop for 24 h. Resultant biofilms were quantified using a crystal violet assay read at 570 nm in a microtiter plate reader (FluoStar Omega, BMG Labtech). Four isolates were used for each assay, and this was performed on two independent occasions in triplicate. *p < 0.05. Error bars represent the ±standard error of the mean.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376416&req=5

Figure 2: Candida albicans biofilm development is inhibited by TTO, T-4-ol, and α-terpineol. Standardized C. albicans (1 × 106 cells/ml) were added to a flat-bottomed 96-well plate and treated with (A) 0.5 and (B) 1 × SMIC50 for 0, 1, 2, and 4 h post incubation. Biofilms were subsequently allowed to develop for 24 h. Resultant biofilms were quantified using a crystal violet assay read at 570 nm in a microtiter plate reader (FluoStar Omega, BMG Labtech). Four isolates were used for each assay, and this was performed on two independent occasions in triplicate. *p < 0.05. Error bars represent the ±standard error of the mean.
Mentions: Inhibition of biofilm formation was assessed for these three compounds at 0.5 and 1 × MIC50 by assessing biofilm biomass. It was shown for all compounds that 1 × MIC50 was able to inhibit biofilm growth effectively when treated at 0, 1, and 2 h post adhesion (8.5−12% biomass compared to control). At 4 h post adhesion, by which time cells had began to form hyphae, treatment with TTO, T-4-ol, and α-terpineol further suppressed biofilm proliferation by 71, 74, and 82% that of the control (Figure 2A). No significant differences were observed between the treatments at each time point. Treatment with 0.5 × MIC50 was overall less effective at inhibiting biofilm growth most notably with TTO, which displayed a time dependent reduction in inhibition, showing a 44% inhibition of cells treated at 4 h (Figure 2B). Both T-4-ol and α-terpineol were significantly more effective against 1 and 2 h cells (p < 0.05), inhibiting biofilm formation by >80%. However, this inhibition was reduced against the 4 h cells (54 and 58%, respectively).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, UK.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus