Tea Tree Oil Treatment of MRSA

Methicillin-resistant Staphyloccocus aureus (MRSA) is a public health problem. The prevalence of MRSA as a pathogen in hospitals and other community settings underscores the importance of eradicating the carriers. As MRSA is not susceptible to commonly used antibiotics, alternative antimicrobial agents are being sought for its eradication. One area of interest involves the use of plant essential oils. Studies indicate the effectiveness of tea tree oil as a treatment for infections of drug-resistant bacteria, including MRSA.

Introduction

This colorized scanning electron micrograph (SEM) depicts a grouping of methicillin resistant Staphylococcus aureus (MRSA) bacteria. Publicly available by the CDC.

Staphyloccocus aureus, more commonly known as staph bacteria or MRSA, is a Gram-positive coccus-shaped anaerobic bacterium pictured in Figure 1.¹ MRSA is a type of staph bacteria that is resistant to beta-lactam antibiotics, such as penicillin, amoxicillin, oxacillin, and methicillin. MRSA often colonizes on the skin or nostrils of healthy individuals, and is relatively harmless at these sites.¹ If S. aureus enters the body (e.g., wounds, cuts), it may cause infections. In such instances, the MRSA infection may range from mild (e.g., pimples) to life-threatening (e.g., infection of bloodstream, joints, or bones). .¹ MRSA is spread through contact and most commonly contracted in public settings, namely hospitals.

Tea tree oil (TTO) is the essential oil derived through steam distillation from the Australian native plant Melaleuca alternifolia. Tea tree oil has been used for centuries as a topical antiseptic. TTO is believed to have antibacterial, antifungal, antiviral, and anti-inflammatory properties.² Although historical anecdotes endorse TTO's medicinal properties, few clinical studies have been conducted to support such claims. Clinical studies, however few, indicate that tea tree oil can treat the skin infection caused by MRSA. Tea tree oil's anti-microbial properties are attributed to its composition of a chemical class known as terpenes, specifically terpinen-4-ol.² Tea tree oil's bactericidal effects make this plant extract a plausible addition or supplement to a MRSA treatment plan.

Tea Tree Oil Composition and Chemistry

Chemical structure of the terpenic derivative, terpinen-4-ol. It is one of nearly 100 tea tree oil compounds identified through gas chromatography-mass spectrometry. Image obtained from Wikimedia Commons

Commercially available TTO is a composition of nearly 100 chemical compounds determined by gas chromatography-mass spectrometry.³ TTO is primarily composed of a class of chemicals called terpenes. Specifically, monoterpenes, sesquiterpenes, and other terpene alcohols dominate this composition. Terpenes are volatile, aromatic hydrocarbons and are typically soluble with nonpolar solvents.² While research indicates that terpene alcohols are generally effective anti-microbial agents, terpinen-4-ol is the specific terpenic compound believed primarily responsible for TTO's anti-microbial activity. Other terpenic compounds in TTO include 1,8-cineole, terpinolene, and α-terpineol, which have less reputable medicinal properties than terpinen-4-ol.²

TTO composition is commercially available in various chemotypes. The most common chemotype is the terpinen-4-ol chemotype where terpinen-4-ol comprises between 30 to 40% of TTO's commercial composition.² A relatively high composition of terpinen-4-ol is more common in commercial production due to its historical medicinal properties.^{2 3}

Treatment and Effectiveness

Efforts to validate the therapeutic properties of tea tree oil (TTO) have yielded in vitro (i.e. laboratory) and clinical studies with results showing eradicated and reduced MRSA infection, respectively. The demonstrated effectiveness of TTO treatment after infection has led to preliminary research regarding TTO application as a way to prevent MRSA infection. While TTO displays in vitro and clinical efficiency, TTO has not been demonstrated to prevent initial MRSA colonization. These studies support the claims upheld by traditional healers that TTO is an effective antimicrobial agent.

Potency

The efficacy of tea tree oil (TTO) against MRSA has been demonstrated in laboratory studies using cultured S. aureus samples. One in vitro study by May et al. showed that MRSA was eradicated after 6 hours of continuous exposure to 5% TTO. These results imply that TTO is able to eradicate MRSA and has strong health implications for clinical usage.

May et al. conducted in vitro experiments to explore the TTO's bactericidal activity in laboratory-grown cultures of MRSA.^citation May found that 99.9% of the MRSA isolate was killed by TTO within 4 hours and that all was killed by TTO within 6 hours.^citation This finding demonstrates TTO's potency against MRSA and suggests that TTO's antimicrobial properties make this a good agent to control MRSA and reduce its transmission among humans.

Clinical Efficiency

The demonstrated efficiency of TTO in eradicating laboratory isolated MRSA cultures led to clinical testing with human patients using products enhanced with TTO.

TTO may be added to commercial products, such as body wash, skin cream, and nasal ointment due to its antimicrobial properties. Such products can be incorporated into a daily regimen to treat MRSA. The clinical efficacy of TTO body wash and creams as a decolonization agent for MRSA has been supported by Caelli et al. and Dryden et al..^{4, 5} Both researchers found that TTO treatment is as effective as the conventional treatment regimen against MRSA infection. These studies indicate that TTO treatment may enhance a MRSA eradication regimen.

Caelli et al. compared the effectiveness of TTO treatment to that of standard treatments against MRSA, as measured by post-treatment MRSA concentrations on the skin and within the nose.⁴ In Caelli’s clinical study, 30 MRSA-infected adult hospital inpatients were randomly assigned to receive either the standard treatment (2% antibiotic nasal ointment and triclosan body wash) or tea tree oil regimen (4% TTO nasal ointment and 5% TTO body wash) for three days. Compared to the standard treatment, the tea tree oil topical regimen reduced or eradicated MRSA infection in more subjects. Despite this optimistic finding, the small sample size prevented this result from being statistically significant. Caelli concluded that TTO treatment was just as effective at eradicating MRSA as the standard medical treatment.⁴

Dryden et al. conducted a similar study regarding TTO's effectiveness against MRSA-related skin infection.⁵ Dryden's clinical study, which involved 236 MRSA patients, found that the daily application of 5% TTO body wash and 10% TTO cream was more effective than standard treatment at clearing skin lesions and variations in skin texture or color associated with MRSA infection.⁵ However, the TTO regimen did not eradicate the MRSA infection entirely.

Although research suggests the efficacy of TTO against MRSA, more clinical studies would have to be performed in order to comprehensively assess TTO's effects on MRSA patients. From these experiments, TTO was deemed to be sufficiently effective, safe, and well-tolerated to be considered part of a MRSA eradication regimen.⁵

Antimicrobial Activity: Cytoplasmic Membrane Damage

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I will create this figure based on research

The target of TTO's antimicrobial activity, and the primary reason for its laboratory and clinical effectiveness, is reported to be the cytoplasmic membrane of MRSA. The bacterial cell membrane physically separates the cell's internal environment from the external environment. It is selectively permeable to organic molecules and ions. As such, it regulates the movement of water and other substances into and out of the cell.⁶ If the membrane is compromised, the cell may rupture due to osmotic pressure. Research indicates that this is the likely mechanism of TTO’s antimicrobial activity against MRSA.

Studies that have examined membrane integrity after TTO treatment indicate that the essential oil disrupts the membrane permeability. If the membrane permeability is compromised, the barrier between the internal and external environment is weakened. Consequently, foreign material would be able to enter the cell more easily while cytoplasmic material would be able to leave it more easily. A study found that TTO treatment disturbed the MRSA membrane permeability in vitro, which allowed propidium iodide, a foreign substance, to enter the cell and potassium ions, part of the cytoplasmic material, to leave the cell.⁷ Another in vitro study demonstrated that TTO-treated MRSA had increased susceptibility to sodium chloride (NaCl), a cell toxin.⁸ From this evidence, researchers believe that TTO alters the cell membrane.

Membrane integrity is key to maintaining the membrane’s normal function. If the membrane is compromised, the cell is unlikely to survive the damage. TTO has been shown to induce lasting membrane damage in MRSA, which represents a plausible mechanism for TTO’s eradication of MRSA.^7,8 However, the details of TTO’s mode of action are under speculation. One model presented by Carson proposes that TTO impairs the membrane’s ability to osmoregulate the cell adequately.⁸ The subsequent rupture of the cell membrane due to osmotic pressure would cause cell lysis.⁸ Since this area of research remains relatively unexplored, more investigation would be warranted to form a theory.

Susceptibility to Antibiotic Resistance after TTO Exposure

The available forms of TTO range from pure oil to retail products for personal health care, home care, and pet care.⁹ Commercial TTO preparations, which may vary in its components' concentrations, provide users more opportunity to apply TTO at ineffective concentrations. The growing use of TTO also implies that a diversity of microbes is coming into contact with sub-lethal TTO concentrations.⁹ There is concern that exposing MRSA to sub-lethal concentrations of TTO, like overexposure to antibiotics, may lead to decreased antibiotic susceptibility (i.e. increased antibiotic resistance). ¹⁰

Similar studies produce conflicting results

Whether TTO exposure decreases antibiotic susceptibility remains a subject of investigation. Evidence has been presented for both sides of this debate. Similar research produced by McMahon et al and Thomsen et al yielded different conclusions.^{11, 12}

In their respective studies, McMahon and Thomsen used similar experimental designs to determine whether exposure of MRSA to sub-lethal TTO concentrations increased its resistance to antibiotics.^{11, 12} Both examined the minimal inhibitory concentration (MIC) of commonly used antibiotics on MRSA before and after the pathogen was exposed to sub-lethal TTO concentrations. They believed that changes in MIC, the minimal concentration of an antimicrobial needed to inhibit bacterial growth, was an adequate indication of MRSA’s sensitivity to the antibiotic. A positive change in MIC suggested increased antibiotic resistance and vice versa.^{11, 12}

Although McMahon and Thomsen’s experiments were conducted similarly, their findings did not match.^{11, 12} McMahon reported that exposing MRSA isolates to a sub-lethal concentration of 0.25% (v/v) TTO increased the average MICs of antibiotics by two-fold or greater.¹¹ McMahon concluded that TTO exposure increased MRSA’s resistance to antibiotics.¹¹ On the other hand, Thomsen reported that exposing MRSA isolates to a sub-lethal concentration of 0.075% (v/v) TTO did not increase the MICs of the same antibiotics by more than two-fold, indicating that any MIC changes were minor.¹² Thomsen concluded that exposure to sub-lethal concentrations of TTO did not contribute to antibiotic resistance.¹²

TTO unlikely to induce antibiotic resistance

It is likely that the exposure of MRSA to sub-lethal TTO concentrations does not increase antibiotic resistance. Thomsen et al defended their stance by pointing out that the numerous replicates in McMahon’s study made minor numerical increases and reductions in MIC statistically significant.¹² A separate study also reported that tea tree oil had little impact on the development of antimicrobial resistance and susceptibility.¹³ These findings suggest that TTO exposure does not alter MRSA’s susceptibility to antibiotics. Further research would be necessary to warrant these findings.

Conclusion

Discovering alternative therapy for the treatment of MRSA is very important as antibiotic resistance becomes more prevalent. MRSA's increasing resistance to mupirocin, the primary antibiotic in standard MRSA eradication treatments, has been noted by Dryden.^{6 Since TTO shows little sign of inducing antibiotic susceptibility in MRSA upon treatment, one alternative treatment is the use of tea tree oil as an antimicrobial agent.}

The application of a TTO regimen is comparable to standard MRSA treatment in eradicating MRSA.^4,5 The reported mechanism for TTO's bactericidal effects is damage to the cytoplasmic membrane, thus making the membrane more permeable to substances, such as water.⁸ Impaired osmoregulation may lead to cell lysis.⁸

Current research focuses on TTO's mechanism of action, safety, and effect on antimicrobial susceptibility. Though cytoplasmic membrane damage is believed to be the major bactericidal effect, the mechanism is still largely unexplored. Other research examines commercial tea tree oil's cytotoxicity if applied topically to human skin.¹⁴ Such investigation would determine the safety of applying TTO on a regular basis and hopefully, the optimal strength of TTO for pharmaceutical formulation.

References

1. MRSA Infection. National Health Service (NHS) Web site. Last revised on 23/09/2011. Accessed on 21/03/2013.

2. Carson, C. F., Hammer, K. A., Riley, T. V. Malalueca alternifolia (tea tree) oil: a review of antimicrobial and other medicinal properties. Clin. Microbiol. Rev. 19, 50-62 (2006)

3.Brophy, J. J., N. W. Davies, I. A. Southwell, I. A. Stiff, and L. R. Williams. Gas chromatographic quality control for oil of Melaleuca terpinen-4-ol type (Australian tea tree). J. Agric. Food Chem. 37, 1330-1335 (1989)

4. Caelli, M., Porteous, J., Carson, C. F., Heller, R., Riley, T. V. Tea tree oil as an alternative topical decolonization agent for methicillin-resistant Staphylococcus aureus. J. Hosp. Infect. 46, 236-237 (2000)

5. Dryden, M. S., Dailly, S., Crouch, M. A randomized, controlled trial of tea tree topical preparations versus a standard topical regimen for the clearance of MRSA colonization. J. Hosp. Infect. 56, 283-286 (2004)

6. Todar, K. "Structure and function of bacterial cells" Online Textbook of Bacteriology. 2012 Published. 15/04/2013 Accessed.

7. Cox, S. D., et al. The mode of antimicrobial action of the essential oil of Melaleuca alternifolia (tea tree oil). J Applied Microbiol. 88, 170-175 (2000).

8. Carson, C. F., Mee, B. J., Riley, T. V. Mechanism of action of Melaleuca alternifolia (tea tree) oil on Staphylococcus aureus determined by time-kill, lysis, leakage, and salt tolerance assays and electron microscopy. Antimicrob. Agents Chemother. 46, 1914-1920. (2002)

9.[www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/herbsvitaminsandminerals/tea-tree-oil Tea tree oil. American Cancer Society Web site. Last revised on 28/11/2008. Accessed on 16/04/2013.]

10. Gilbert, P., McBain A. J. Potential impact of increased use of biocides in consumer products on prevalence of antibiotic resistance. Clin. Microbiol. Rev. 16, 189-208 (2003)

11. McMahon, M. A. S., Blair, I. S., Moore, J. E., McDowell, D. A. Habituation to sub-lethal concentrations of tea tree oil (Melaleuca alternifolia) is associated with reduced susceptibility to antibiotics in human pathogens. J. Antimicrob. Chemother. 59, 125-127. (2007)

12. Thomsen, N. A., Hammer, K. A., Riley, T. V. Belkum, A. V., Carson, C. F. Effect of habituation to tea tree (Melaleuca alternifolia) oil on the subsequent susceptibility of Staphylococcus spp. to antimicrobials, triclosan, tea tree oil, terpinen-4-ol and carvacrol. Int. J. Antimicrob. Agents. 41, 343-351. (2013)

13. Hammer, K. A., Carson, C. F., Riley, T. V. Effects of Malaleuca alternifolia (Tea Tree) essential oil and the major monoterpene component terpinen-4-ol on the development of single- and multistep antibiotic resistance and antimicrobial susceptibility. Antimicrob. Agents Chemother. 56, 909-915 (2012)

14. Loughlin, R., Gilman, B. F., McCarron, P. A., Tunney, M. M. Comparison of the cidal activity of tea tree oil and terpinen-4-ol against clinical bacterial skin isolates and human fibroblast cells. Letters in applied microbiology. 48, 428-433 (2008)

[Edited by Karen Leung, a student of Nora Sullivan in BIOL187S (Microbial Life) in The Keck Science Department of the Claremont Colleges Spring 2013.