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Allicin: an antibacterial agent derived from garlic

Ronald R Cutler
PhD MSc(Lond) MSc(Cran) MIBiol CIBiol FIBMS DMS
Senior Lecturer
Department of Biosciences
University of East London
E:R.Cutler@uel.ac.uk

Multiple antibiotic-resistant bacteria such as MRSA (methicillin-resistant Staphylococcus aureus) are a major problem in hospitals and the community. In a publication, "What are the choices for treating MRSA?", the authors concluded that: "Only vancomycin as a systemic agent and mupirocin as a topical agent offered reliable treatment against MRSA".(1) They also highlighted that, since 1990, reports of mupirocin resistance had increased.
Given the failure of conventional antibiotics to control and eradicate these microorganisms, and the lack of alternatives, some researchers, ourselves included, have turned to antimicrobial agents from plants (phytochemicals) to combat these bacteria.
The historical use of allium vegetables such as garlic, chives and onions to treat a wide range of ailments dates back over 3,000 years and is mentioned in the Egyptian Codex Ebers Papyrus (1550 BC).(2) Garlic powders, extracts and oils were used by many ancient civilisations to treat a wide variety of disorders, such as heart disease, headaches, bites, intestinal parasites, tumours and for the local treatment of wounds.(2,3)
The main antibacterial and biologically active component in garlic is an organosulphur compound called allicin. When the garlic bulb is bruised or crushed, alliin, the precursor of allicin, comes into contact with the enzyme alliinase to form allicin (see Figure 1). It was not until 1944, however, that Cavallito and colleagues identified allicin as being responsible for the remarkable antibacterial activity of crushed garlic cloves.(4)

[[NIP04_fig1_64]]

Recent studies investigating the biological effects of garlic extracts have found considerable variation in the quantities of allicin compounds in garlic products.(5) One problem is that natural allicin is normally unstable.  Without a pure stable allicin product, much of the research into the antibacterial activity of these compounds is open to error.
Under different conditions allicin will break down into a veritable panacea of biologically active components, each with different biological activities (see Figure 1).(6)
The activity of allicin is related to its reaction with thiol-containing enzymes. Its major action in bacteria is thought to be its effect on RNA synthesis.(7) Compared with many of the "frontline" antibiotics used today, allicin (C6H10OS2) is a small, relatively simple molecule (see Figure 2). This aids its ability to penetrate bacterial cells quickly.

[[NIP04_fig2_64]]

Previously we compared the activity of crude garlic extracts and pharmaceutical preparations against a range of clinically isolated pathogens, including Staph. aureus. We found virtually no antibacterial activity in any of the commercially prepared product:, we observed activity only in the aqueous crude extract. As many of these products used a variety of extraction methods to isolate active agents from the garlic, we then tested various extraction methods to determine which was the most effective at producing an antistaphylococcal agent. We found that aqueous extraction methods produced a higher antimicrobial activity than any of the oil-based methods tested.(8)
Our research is currently directed towards producing a topical cream active against MRSA. The major problem with this is that pure allicin has been variously described as:

  • Highly volatile.
  • Poorly miscible in water.
  • Having the odour of freshly crushed garlic.

Novel improvements in extraction and purification methods using a cold aqueous extraction method have produced a natural nonsynthetic allicin in a stable pure form (Allimax, marketed by Health Perceptions Ltd). Our initial laboratory studies have demonstrated that this allicin product can be incorporated into an aqueous cream and retains its activity for up to six months.(9)
One of the most exciting findings of our research is the activity of allicin against mupirocin (Bactroban, GlaxoSmithKline)-resistant MRSAs. Mupirocin (pseudomonic acid, isolated from the bacterium Pseudomonas fluorescens) was introduced in the UK in 1985. It has proved to be an effective treatment for staphylococcal skin infections and plays a crucial role in the control of MRSA outbreaks. However, strains resistant to mupirocin were recognised from its introduction. Mupirocin-resistant strains have now been isolated in many different countries, from patients colonised with MRSA.(1)
Mupirocin resistance can be separated into two main forms - intermediate-resistant and resistant. We have demonstrated that allicin is active against both groups of strains.(10) Measuring the zone of inhibition of growth around a concentration of antibacterial agent is a common hospital laboratory test to demonstrate resistance or susceptibility to an antibacterial agent (see Figure 3). Normally with a zone of inhibition of 12mm (diameter) or more, the organism is considered susceptible to the agent under test (see Figure 4).

[[NIP04_fig3_66]]

[[NIP04_fig4_66]]
 
Various cream formulations containing allicin have now been tested in our laboratories. A new formulation based on an aqueous cream has been found to be ­very effective against MRSA, and the organosulphurous smell normally associated with biologically active garlic extracts has been masked.(9) Initial trials testing for skin sensitivity using a modification of the FDA challenge test (see www.healthatoz.com/ atoz/ Test Procedures/TPAllergy.html) have shown that, at the proposed concentration of 500ppm, no skin reactivity has been demonstrated, but further skin sensitivity trials are taking place.
 
The future
For the immediate future, following skin sensitivity trials, it is intended to carry out clinical trials to establish the effectiveness of allicin to reduce nasal and skin carriage of MRSA. If successful, then a safe natural alternative to mupirocin for the topical treatment of staphylococcal infections and carriage will be available.

References

  1. Schmitz F, Jones ME. Antibiotics for treatment of infections caused by MRSA and the elimination of MRSA carriage. What are the choices? Int J Antimicrob Agents 1997;9:1-19.
  2. Budge EAW. Doctors and physicians in the ancient world. Chicago: Ares Publishers; 1978.
  3. Majno G. The healing hand: man and wound in the ancient world. Cambridge, MA: Harvard Press; 1975.
  4. Cavallito CJ, Bailey JH. Allicin, the antibacterial principal of Allium sativum. J Am Chem Soc 1944;66:1950-4.
  5. Lawson LD, Wang Z-Y J, Hughes BG. Identification and HPLC ­quantitation of the sulphides and dialk(en)ylthiosulphinates in ­commercial garlic products. Planta Med 1978;57:363-70.
  6. Agarwal KC. Therapeutic actions of garlic constituents. Med Res Rev 1996;16:111-24.
  7. Ankri S, Mirelman D. Antimicrobial properties of allicin from garlic. Microbes Infect 1999;2:125-9.
  8. Cutler RR, Townsend T, Sweeney D, Mukimbri E. Antibacterial activity of garlic extracts against MRSAs and gram negative rods. Br J Biomed Sci 1999;57:43.
  9. Cutler R, et al. The development of a novel natural, topical agent, active against MRSA. Br J Biomed Sci 2002; (in press).
  10. Cutler R, et al. Proceeding from the Interscience Congress on Antimicrobial Agents and Chemotherapy, Chicago 2001: Abstract 2279.

Resources
Health Perception
W:www.health-perception.co.uk