On the specificity of phages

One of the main objections that I have heard to the use of bacteriophages as therapeutic agents is that phages tend to be very very specific. Each phage usually only attacks one type of bacteria, e.g a bacteriophage for a certain type of e. coli will usually only attack that specific e. coli type and no other bacteria. As there are a large number of different varieties of e. coli (and indeed many other pathogenic bacteria), this specificity could be a problem for targeting infections.

(as an aside, phages are often so specific that they are used to 'type' bacteria. If you find a bacteria in, say, sewage, one way to find out what it is is to attack it with different phages and see which one digests it. This can give a very specific pinpoint of what bacteria you have).

The usual response to the problem of phage specificity is to suggest that a cocktail of phages can be used, one for each potential type of attacking bacteria. In some ways, this can be even more useful for controlling infection; a broad-spectrum antibiotic will knock out any bacteria it comes across while a cocktail of phages will target specifically the unwanted ones. Going back to the example of e.coli: there are lots of e. coli living happily in your gut. If a pathogenic strain gets in, the phage therapy that you are given could be designed to target just the pathogens, rather than the bacteria that are already there (and are necessary for correct digestion).

I was quite surprised therefore to come across this paper while randomly searching PubMed (as you do). Maddeningly, there seems to be no way to get the the actual paper, but what it says is that a phage has been found (and named KVP40 for those interested) which has quite a wide host range. Not only does it attack a variety of Vibrio phages (both pathogenic and non-pathogenic) it also is able to attack a Photobacterium as well (Photobacterium leiognathi). A further paper states in the introduction that the receptor that the Vibrio uses to bind to the surface of its bacterial hosts is the OmpK outer membrane protein. I am not entirely certain what this protein does, but I have found that it is involved in vibrio bacterium immunoprotection and is also present in the photobacterium species. As it elicits a large immune response, it is also being considered as a vaccination, if not in people then at least in the yellow croaker (which is a fish).

And this is where phage therapy could come in useful. I don't know how dangerous the vibrio phage is in yellow croakers (this paper seems to make quite a thing of it, but that may be linked to funding purposes). With enough commercial interest (if it hasn't already happened), it's only a matter of time before someone starts looking for an antibiotic for Vibrio harveyi, the vibio species that attacks the poor fish. Essentially this means that a large amount of time and effort will be spent looking for something that will attack the vibrio species, find it on the basis of the OmpK protein, and then destroy it.

Completely ignoring, of course, the fact that such a thing already exists, in the form of the KVP40 vibriophage. There are millions of them floating around in the sea. They've been isolated as well, in pure phage form.

More people need to be working on this stuff...