Welcome to the Microbiology Information

Did you know that bacteriophages which are commonly known as “phages” are naturally occurring viruses that infect and kill bacteria with very high specificity.

They do this by attaching to the surface of the bacterium, replicating inside, and eventually destroying their host. Most importantly, bacteriophages are specific for only one type of bacteria so the normal flora are left intact. Because replication is so rapid (one phage can produce 2 billion offspring in 2 hours) bacteria have little opportunity to develop resistance. In addition, once the target bacteria have been destroyed, the phages are no longer capable of reproduction, and subsequently disappear through natural processes, leaving no harmful residues. This environmentally friendly characteristic of phages is a major advantage when compared to conventional antibiotic use, where toxic residues have led to many problems. As such they represent a formidable, yet underutilised weapon in our constant war against bacterial infections.

Bacteriophage Therapy is the practical application of these very powerful lytic viruses to a bacterial infection, whether in animals, fish or even plants. The concept may appear novel but the fact is that it has been used for over 85 years in Eastern European countries like Georgia and Poland where it became part of the standard health care to treat burns, wound infections and gastrointestinal disorders.

Bacteriophages were discovered independently by two scientists between 1915 and 1917, more than 20 years prior to the isolation of Penicillin.

In 1915, Frederick Twort reported an “ultracosmic virus that somehow killed bacteria in solution”. Two years later Felix d’Hérelle a French-Canadian biologist identified and coined the name bacteriophage, meaning “bacteria eater”. Highly excited by the efficiency of the viruses against Shigella bacteria, d’Hérelle continued his studies on phages and was the first person to realise the potential of bacteriophages as therapeutic agents. In 1919 for the first time in history, he treated a 12 year old boy with severe dysentery; within 5 days of treatment the boy was completely cured.

After d’Herelle’s first successful use of phage therapy, other scientists around the world became interested in the new phenomenon and its potential as a therapeutic method.

Europe and the United States began to produce their own phages on a large scale for the medical treatment of cholera, typhoid fevers and bubonic plague. In 1932 in India alone, 191,000 vials of bacteriophages were used for the treatment of cholera. However, at the time, very little was known about phage biology and the very high specificity required for a successful treatment was poorly understood. Many famous scientists, including Bordet, disagreed violently with d’Herelle that the phenomenon was caused by a virus and argued that it was an enzyme or an active component present in the solution which caused the observed effect. Others thought that the solution simply stimulated the immune system, facilitating the healing process. Due to the resulting confusion doctors often used mismatched phages with a corresponding lack of success. Companies manufacturing the phages compounded the problem by making exaggerated claims and supplying poor quality products. It was hardly surprising that negative reports began to appear in the literature questioning the effectiveness of phage therapy.

By the late 1940’s, mired in controversy and with the widespread availability of penicillin and other broad spectrum antibiotics, phage therapy fell into decline and eventually vanished from the Western scientific radar, except as a bacteriology typing tool and as a platform for molecular biology. After all, the successful use of phage therapy depended heavily on the correct identification of a particular bacterial pathogen, plus the skills required for production. Why bother when the “magic bullet”, penicillin, came as a white powder, had broad spectrum of activity and was cheap and highly effective?

Fortunately, scientists in the former Soviet Union and various Eastern European countries, including Georgia and Poland persevered with their studies of phages. In Georgia, The Eliava Institute has been producing phages for the treatment of patients since 1930 and has recently attracted the attention of scientists anxious to benefit from their vast experience in the treatment of bacterial infections. However, despite the fact that phage therapy has been widely used and refined for over eighty years, it is still considered by Western science to be an experimental field because much of the development preceded the modern, more stringent regulatory standards of western pharmaceutical products.

A number of research institutions and companies around the world have taken up to the challenge of re-introducing bacteriophage therapy to our markets for the treatment of human, animal and agricultural bacterial infections. Initial studies have confirmed many of the original scientific observations. As a result, clinical trials have been set up in England, Germany and the United States to study the efficacy of phages. In the agricultural sector, the first phage based product for the use on tomatoes and pepper crops has received a commercial registration from the U.S Environmental Protection Agency (EPA). The FDA has also granted approval for a new core product of 6 lytic phages as a food additive in meat and poultry products to prevent infection with Listeria monocytogenes, a bacterial pathogen that affects more than 2500 people annually, especially pregnant women, newborns and immune-depressed individuals. In Wroclaw, the Institute of Immunology and Experimental Therapy (IITD) has been granted authorization to treat people with phages in cases where all else had failed.

The encouraging developments show that Phage Therapy has the potential to be a useful alternative antimicrobial therapy. However, much work still needs to be done to optimise the treatment protocols and to provide solid evidence on the safety of the treatment to the highest standards. Nonetheless, with the inevitable rise in antibiotic resistance and the diminishing pipeline of new antibiotics, phage therapy may prove to be a valuable and timely weapon in the fight against bacterial infections.

About the authors
Dr. Anthony Smithyman completed a PhD on Bacteriology and Immunology at Glasgow University in 1978. For the past 20 years he has managed Cellabs Pty, a Sydney-based diagnostics company, which specialises in Tropical and Infectious diseases.

Sandra Morales is a Microbiologist working for Special Phage Services Pty Ltd, Australia’s first phage-therapy company. She is also a PhD student in the University of Technology of Sydney and is currently undertaking an investigation of the potential use of bacteriophages in the treatment of antibiotic resistant infections. The project includes the screening of hundreds of Australian isolates against a broad collection of bacteriophages and studying their efficiency and potential for viable products.

References
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Kutter, E. & Sulakvelidze, A. (2005) Bacteriophages Biology and Applications. United States of America. CRC.

Noskin, G MD. et al. (2005) The Burden of Staphylococcus infections on Hospitals in the United States: An analysis of the 2000 and 2001 Nationwide Impatient Samples Database. Arch Inter Med, 165(1):1756-1761

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Sulakvelidze, A., Z, A. and G, M. (2001) Bacteriophage Therapy: Minireview. Antimicrob Agents Chemother, 45, 649-659.

Sulakvelidze, A. (2005) “Phage therapy: an attractive option for dealing with antibiotic-resistant bacterial infections.” Drug Discovery Today 10(12): 807-809.