Coming of age for the bacteria-eaters?

The most abundant biological entity on the planet is the bacteriophage (literally bacteria-eater) – and yet there have been long debates over whether they are really ‘alive’ – see here. Bacteriophages are viruses that infect and kill bacteria and are sometimes simply called ‘phage’. They attach to their bacterial host, inject their DNA and ‘take over’ the host, making the bacterial cell in to a bacteriophage factory. Once the progeny bacteriophage are assembled, they burst out of the bacterium, killing it and releasing the phage to go on and infect more bacteria.

And now for some very large numbers  – It has been estimated that there are somewhere in the region of 10, 000,000,000,000,000,000,000,000,000 (10³¹) phage on the planet at any one time – that is many more than the estimated 10, 000,000,000,000,000,000,000,000 (10²⁴) stars in the universe!  Phage are also estimated to completely turn over the bacterial population of earth every 24hrs! So we know that phage are important ecologically, and that they are engaged in an ‘arms race’ with their bacterial hosts – bacteria trying to resist infection, and phage evolving to overcome this resistance.

Since their discovery in the early 20^th century phage have been used as a research tool –they were central to the development of molecular biology in the mid to late 20^th century. It has always been proposed that they could be used as ‘antibiotics’ due to their ability to kill bacteria causing infections in humans and animals. They have lots of advantages – they are highly specific for their bacterial host, often even for one specific type of bacteria. They cannot infect anything other than bacteria. They multiply in their host to produce more phage, so if the infection is large, the bacteriophage population will increase as they have more ‘food’. Bacteriophage reproduce rapidly, often within 20-40 minutes depending on their bacterial host, and they are cheap to grow and can be mixed and stored easily as ‘cocktails’ of phage to treat a range of bacterial infections.

So why have we not used them already? Well there have been trials in former USSR states such as Georgia with good success, although the work was published in Russian during the cold war and was not easily accessible to the wider world. In the EU and North America there has been resistance to widespread use of phage in humans due to too many unknowns. Delivery to infections has been difficult to regulate and there is still much to learn about basic phage biology.

Recently there were reports from the University of Leicester (here and here) that work from Professor Martha Clokie and her team has shown that cocktails of phages could be used to treat pigs, where there is a risk of infections such as Salmonella being transmitted to humans. Professor Clokie’s team were able to develop a powdered version of a phage cocktail that could be added to pig food, targeting and reducing the number of harmful bacteria in the pig’s gut, which will ultimately reduce human infections via the food chain.

The work is yet to be published, but trials are ongoing.  Prof Clokie is confident that the treatment offers a good alternative to conventional antibiotics. This is a good thing, as it is clear that the use of antibiotics in agriculture is a driving force behind the emergence of antibiotic resistant infections in humans.  One of the recommendations of the ‘O’Neill Report’ was to reduce the use of antibiotics in agriculture.

This work is important because it potentially paves the way for the use of phage therapy in humans.  Success in animals and reduced numbers of pathogens in food animals could then help to provide the impetus for trials in humans of similar cocktails.