Bacteriophage- the answer to Antibiotic Armageddon?  

Ken Donaldson, Senior Research Fellow at Surgeons’ Hall Museums, tells us why we are facing an “Antibiotic Armageddon” and how Bacteriophages could be the solution to this catastrophic problem.  

Most people will have heard about the development of antibiotic resistance in bacteria, sometimes called ‘Antibiotic Armageddon’. This refers to the fact that some common infectious bacteria have developed resistance to antibiotics. Antibiotics work by killing bacteria whilst not harming our own cells, it’s as simple as that.  But in the case of antibiotic-resistant bacteria, they are not killed by a course of antibiotic and it has no effect in stopping the infection. This raises the dreadful spectre of a return to the pre-antibiotic era, when people suffered chronic infection of the lungs, skin, gut, urinary tract and died from sepsis, with no effective treatment.

Reasons for the rise in antibiotic resistance in bacteria that previously were treatable with antibiotic, include over-prescribing of antibiotics, intensive farming with large-scale use of antibiotics and careless use of antibiotics. At the moment the search is on to find new antibiotics to replace the ones to which bacteria have become resistant. However, the pharmaceutical companies do not stand to make much profit from finding new antibiotics and so there is no concerted effort in this direction. We are therefore faced with the Antibiotic Armageddon scenario, with 10 million deaths worldwide by 2050 from untreated infection, costing £66 trillion pounds. Even now 25,000 people die each year in European hospitals as a consequence of antibiotic resistance to 5 common resistant bacteria, at a cost of £1 billion.

There are however things other than antibiotics that kill bacteria. Chief amongst these is a whole invisible world of viruses that infect bacteria and kill them. These tiny microbes are called Bacteriophages, or Phages, which means ‘bacteria eaters’ and their existence has been known for more than 100 years. They have no effect whatsoever on human cells, but they can and do kill bacteria. They are becoming a focus of hope in some quarters, since they represent an opportunity of treating infection by killing antibiotic resistant bacteria in the infected people.  Phages are found everywhere there are bacteria and they live in ecological balance with bacteria, infecting them, living inside them and, most importantly, killing them. Phages are very specific in infecting and killing bacteria, meaning that a single type of Phage only infects and kills one single type of bacterium. So they are much more specific than antibiotics, where any one antibiotic can kill many types of bacteria.

 

FIG 1
Diagram of a phage infecting  a bacterium. The phage is not to scale and would be about 10 times smaller as shown in the actual photograph below..
FIG 2
High power electron microscope image of about 20 phages at the top, attaching to and infecting a single bacterium

Phages were first suspected to exist by Ernest Hankin in 1896 and then fully identified during the First world war by British bacteriologist Frederick Twort in London and the French Canadian microbiologist Felix d’Herelle in Paris. Almost immediately the potential therapeutic use of phages in infection was recognised and treatment trials were undertaken, principally in Eastern Europe and Russia. However these studies were not well documented and then stalled with the advent of antibiotics in the mid-20th century, since antibiotics seemed like a better investment as they generally kill across many bacterial types and are easier to make and handle than preparations of phage, which are living organisms after all.

Once a phage encounters the bacterium that it recognises, it attaches to the surface by a base plate and feet that make it look like a small spacecraft homing to a mother-ship (See figure). Guided by the spidery-looking ‘legs’ the phage attaches to the outside of the bacterium via the base plate. The Phage head contains the bacterial DNA which is injected into the bacterium through the  tail and this integrates into the bacterial DNA, making more phages and eventually killing the bacterium and releasing Phages to infect other bacterial cells.

In therapeutic use the Phages have to be chosen to match the bacterial type infecting the affected person. The Phages have no effect on the infected individual’s cells but may kill the infecting bacteria, leading to the end of the infection and recovery. More recently small-scale clinical trials have been carried out which look promising and treatment with phage has led to recovery in individuals infected with antibiotic resistant bacteria where all other treatment options had failed.  If successful and shown to be safe in large scale clinical trials and the technical problems of obtaining live phage in an easily delivered form can be solved, then perhaps we may look forward to delivery from the feared  Antibiotic Armageddon.

 

On the 10th of June we will be joined by Dr. Till Bachmann and Cafe Scientifique for a discussion on Anti-Microbial Resistance.For further information and to book your space visit our Eventbrite page.

 

 

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