As a general rule in life there is always a bigger fish – for every predator there is a bigger one lurking that is ready to eat it. However it is also worth remembering that there is usually always a smaller fish as well; for every small irritating parasite there is something that can infect it. Bacteria are no exception.
Bacteriophages are viruses that infect bacteria. They come in two different flavours; latent phages, which incorporate themselves into the bacterial genome and lie in wait, and lytic phages which infect bacteria, take over the cell, fill it with their offspring and then all burst out of it like the baby alien in Alien. While latent phages are fascinating for geneticists (not least because they provide a way of getting DNA into a bacteria) lytic phages are even more fascinating for people trying to kill bacteria, as they provide a way of destroying the cells.
The advantage of bacteriophage as an antibacterial treatment is that they are more specific and accurate than antibiotics; antibiotics will simply kill most bacteria they come across whereas bacteriophage are specific for certain species. And unlike an antibiotic, which has to flood your system to have any effect, bacteriophage will replicate specifically within the invading bacteria at the point of infection.
On the other hand, just like any other antibacterial, the bacteria will eventually develop resistance towards the phages. If you attack a bacterial infection with one phage strain specific to that bacteria than very soon the bacteria will be able to withstand attack. One way to counter this is to blast the bacteria with many different types of phage that work in slightly different ways. Researchers working on the bacteria Klebsiella pneumoniae came up with a streamlined method for creating a ‘bacteriophage cocktail’ for a specified bacterial invasion. The cocktail contains different strains of phage, all of which can attack the bacteria in different ways, making it harder for the bacteria to develop resistance against any one of them.
Although the diagram above shows a ‘standard’ bacteriophage, there are small differences between strains that can be seen under an electron microscope. Some have different shaped heads, or differently ordered tails. Some of the tails are straighter, or longer, than others. Using the different phage morphologies, the researchers isolated three different strains, and then confirmed the difference by looking at which strains of bacteria they all infected. Although there was substantial overlap between the bacteria they could kill, there were differences between each phage strain.
This three-phage cocktail was shown to be more effective than a monophage therapy in clearing the bacterial infection, and it also worked effectively at much smaller doses. The three-phage mix killed the bacteria much quicker, allowing less time for resistance to develop, and the researchers put forward that they might even have a synergistic effect – one phage lowering bacterial defences and allowing another to more effectively invade.
The development of phage cocktails, either to be taken instead of antibiotics, or to be taken with a lower dose of antibiotics, has the potential to be an incredibly useful area of research. At the moment the few phage cocktails that are used in come countries seem to be a rather haphazard mix of phage strains. A technique for quickly establishing strains for an effective antibacterial-cocktail would be a great help for phage technology and antibacterial treatments.
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Ref: Gu J, Liu X, Li Y, Han W, Lei L, Yang Y, Zhao H, Gao Y, Song J, Lu R, Sun C, & Feng X (2012). A method for generation phage cocktail with great therapeutic potential. PloS one, 7 (3) PMID: 22396736