A Review of the Antibacterial Action of Tea Tree Oil

The use of tea tree oil (TTO) in complementary and alternative medicine has surged in popularity in recent years. Available both as the pure, undiluted oil or as an active component in medicinal and cosmetic products, TTO’s antibacterial properties have garnered significant attention. This article will detail the exact activities it exerts and the mechanisms of action of its antibacterial properties.  

Background

Melaleuca alternifolia, otherwise known as tea tree, is a native Australian shrub/small tree from which the essential oil is derived.

Composition and chemistry

Tea tree is comprised of terpene hydrocarbons- mainly monoterpenes, sesquiterpenes and associated alcohols. Terpene hydrocarbons are unsaturated hydrocarbons, formed by joining several units of 2-methylbuta-1,3-diene.

Terpenes are aromatic, volatile hydrocarbons. They are sparingly soluble in water and are miscible with some nonpolar solvents. There is some variation across different batches so the composition of TTO is regulated by a set of international standards which sets maximum/minimum values for the 15 components of the oil. It specifies that the oil must be primarily composed of terpinene-4-ol which is the main active agent and outlines the ideal physicochemical properties and criteria the chemotype must possess.

There have been 6 chemotypes given: terpinene-4-ol, terpinolene and four 1,8-cineole chemotypes. The terpinene-4-ol chemotype has levels of terpinen-4-ol of between 30-40% and is the chemotype used in commercial TTO. The upper limit for 1,8-cineole is 15%. The role of 1,8-cineole in acting as an irritant is debated upon as historical anecdotal evidence suggests this but recent data does not support this. However, its use is still cautioned as its levels are typically inversely proportional to terpinene-4-ol levels, which is the component that gives TTO its beneficial effects

Extraction of oil

Tea tree oil is produced by steam distillation of the leaves and terminal branches of the plant. After condensation, the oil which is clear to pale yellow in colour is separated from the aqueous distillate. The yield of oil is usually 1-2% of wet plant material weight. There are other extraction methods such as using microwave technology but none have been used on a commercial scale.

History of use

The earliest use of M.Alternifolia for this purpose was by the Bundjalung aborigines of northern New South Wales, where they crushed the plant’s leaves and inhaled them to treat coughs/colds or applied them on wounds. The first reports of these properties were published in a series of papers by Australian chemist Arthur Penfold in the 1920s and 1930s. He compared TTO with then-gold standard disinfectant carbolic acid or phenol; TTO was found to be 11 times more active. However, by modern scientific standards the data provided by these studies would be deemed anecdotal and thus hinder its reliability.

TTO’s physical properties have impeded further evaluation of its antibacterial activity-for example it is sparingly soluble in water, which limits miscibility in test media.

Mechanism of antibacterial action

Tea tree oil’s hydrocarbon structure and lipophilicity were used to deduce its mechanism of action. Hydrocarbons partition preferentially into biological cell membranes and harm their essential functions. TTO and its relevant components were thought to behave in this way. This was supported by studies showing TTO permeabilises into model liposomal systems. TTO treatment of S.Aureus (staphylococcus aureus) caused the leakage of potassium ions and inhibition of cellular respiration. S.Aureas is a gram-positive bacterium that can cause a range of infections such as skin infections, pneumonia and sepsis.1,8-cineole was theorised to permeabilise bacterial membranes and allow the entry of more active components. TTO is mostly bactericidal but at lower concentrations may be bacteriostatic.

While broad-spectrum membrane disruptors make cross-resistance less common than single-target synthetic antibiotics, repetitive exposure to sub-inhibitory concentrations of TTO can induce transient, non-specific tolerance or altered gene expression (e.g. upregulating efflux pumps) in pathogens like Staphylococcus aureus and Pseudomonas aeruginosa. 

A 2018 study conducted in Bangladesh compared the effects of TTO, eucalyptus oil and lemongrass oil on 10 different bacteria and aimed to find their inhibition rate. It was done against ten pathogenic bacteria (Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, Proteus vulgaris, Aeromonas hydrophila, Escherichia coli, Streptococcus pneumoniae, Bacillus subtilis, Klebsiella pneumonia and Streptococcus agalactiae) via the methods of broth dilution and agar well diffusion.

Two tubes were prepared, one with 5ml of brain heart infusion broth (BHIB) and another with a mixture of 4ml of BHIB with 1ml of the oil. 900ul of saline solution was added to this to make 6 tubes of broth and 4 tubes for broth with oil. Then 100ul of bacterial suspension from a broth were added to each tube. After incubation 100ul of the samples were spread on an agar plate with nutrient agar, and these were incubated at 37 degrees for 24 hours. The colony forming unit for each plate was counted and compared and the rate of inhibition for every diluted tube was calculated to find the actual inhibition percentage.

TTO proved to be the strongest antimicrobial agent in this study, achieving a quick killing time of under 60 minutes. The highest inhibition zone was 36.3mm and was yielded with TTO against A.Hydrophila, which was 1.1 times stronger than the control antibiotic cefepime. TTO also showed significant action against all the pathogens involved in this study, in contrast to the other two oils. This is not the first study showing the inhibitory effects of TTO against pathogens. Carson et al (2006), Carson and Riley (1995) and Cox et al (2005) showed TTO having inhibitory effects on bacteria with E.coli. Lee et al (2013) showed TTO displayed dose-dependent inhibitory effects against the proliferation of P.Acnes and S.Aureus, with stronger inhibitory effects against P.Acnes. 

Limitations and caveats

The concentration of tea tree oil is the main determining factor for its efficacy. At concentrations under 1%, TTO is bacteriostatic, meaning it slows down the rate of bacterial growth but cannot reliably kill bacteria. Studies usually use concentrations of 1%, 2% or even higher. Clinical trials that showed benefit for skin conditions such as acne used formulations with minimum 5%. 

Topical application of TTO at high concentrations can cause adverse reactions like skin irritation, allergic contact dermatitis, erythema-like reactions and systemic hypersensitivity reactions. Interestingly, the dermatitis caused by TTO may be due to the formation of products of monoterpene oxidation such as peroxides, epoxides and endoperoxides when the oil is exposed to heat, light or oxygen. Oral administration of TTO has suggested more severe reactions like central nervous system depression, ataxia (a neurological condition characterised by difficulty in coordination) and pneumonitis. The International Fragrance Association has classified pure tea tree oil as harmful and as such it is labelled with warning labels such as H302 (harmful if swallowed), H315 (irritating to skin) and H304 (may cause lung damage if swallowed). 

Conclusion

The weight of evidence suggests tea tree oil does possess antibacterial activity, with terpinene-4-ol demonstrating its characteristic mechanism of membrane disruption across a wide range of pathogenic bacteria. Its bactericidal action at low concentrations and an apparent lack of susceptibility to antibiotic resistance mechanisms make it a pharmacologically interesting compound, especially in a climate of increasing antimicrobial resistance.

However, the current evidence does have limitations. Most studies have been conducted in vitro and translating these to clinical efficacy in humans is not straightforward. Concentration being the determining factor is a significant constraint as the concentrations needed for reliable bactericidal activity are often those which pose adverse effects such as skin irritation. The variation in composition across different commercial products also complicates direct comparisons across studies. 

Nevertheless, tea tree oil is positioned at an interesting intersection of ethnomedicine, herbal remedies and modern pharmacology and medicine. Further thorough clinical trials at standardised concentrations are needed before stronger therapeutic claims can be brought forward and justified. 

Written by Emaan Alvi

Related articles: Medicinal manuka / Natural substances as treatment to infection