Since I’m going away for a long weekend, I’ll leave you with this post about phage therapy from the archives.
So Aetiology, in her new digs, wants a post. Well, here’s one, inspired by a comment: phage therapy. “Phage therapy” is short for bacteriophage therapy. Bacteriophage are viruses that kill bacteria (literally, “bacteria devourers”). The basic concept of phage therapy is to introduce the phage into an infected patient. The phage infect the bacterium-an infection of an infection! Then the phage multiply within the bacterium, lyse (explode from the inside) the host bacterium and move onto the next bacterium. Essentially, you have a self-manufacturing antibiotic.
So that’s the concept, but does it actually work? Typically, the phage are administered in a pH buffered solution and ingested (the pH buffer prevents stomach juices from degrading the phage). They are typically not administered intravenously, since it’s thought that bacterial debris from the phage manufacturing process will cause an immune system response (note: phage are cultured by growing them on bacterial cells; the lysed cells-the debris-are present in the phage solution). However, they are effective against most sepsis (bloodstream) infections anyway (it’s not entirely clear how they get into the bloodstream). Success rates are typically equivalent to traditional antibiotics. Phage therapy has two other advantages: it’s very cheap, and the phage are far more robust to heat than some antibiotics (no refrigeration needed).
There can be some treatement side effects. Often, when exposed to phage, bacteria enter what I call ‘panic mode’ (that’s a highly technical term) where the bacteria produce every nasty thing they can including all sorts of toxins (if they have toxin-producing capability). This can happen with traditional antibiotics too; however, the presence of traditional antibiotics can also lower toxin production.
In terms of therapeutic use, right now, they are not being used outside of experimental medical settings (and the occasional bout of desperation). The Soviet Union, and later, Russia used to produce phage for widespread clinical use. The production facilities are located in the Georgian Republic, and due to the civil war, are essentially non-operative (an aside: the Georgian phage researchers should be an inspiration to scientists everywhere. They are real-life Arrowsmiths, often working without pay and refusing to abandon their institute despite having minimal resources, or for that matter, heat or electricity. Despite this privation, they still manage to treat and cure some people, and conduct some research).
Finally, would resistance be a problem? I’m not sure. Resistance to phage can evolve (and depending on the phage, can be quite prevalent). On the other hand, resistance to a phage in a particular bacterial species probably wouldn’t be able to spread (the known transmissible systems appear to be very phage specific).
Ultimately, the advantage and the disadvantage of phage therapy is that is a narrow spectrum treatment: a particular phage works against a certain species (or even a subset of a species). The disadvantage is that you have to know something about the infectious bacterium such as what species it is, and such diagnoses can take several days-time many patients do not have. On other hand, the evolution of resistance will be limited to a much smaller group of bacteria (and you can always try to isolate, or evolve in the laboratory, new phage, making the development process substantially cheaper).
Phage therapy won’t be a magic bullet. But, hopefully, phage therapy will become one more tool we can use to stop the evolution of antibiotic resistance.
This is what I’m working on! Phage therapies for Campylobacter.
Just one thing you missed and I’d like to point out (if you don’t mind) concerning resistance. Bacteria can develop resistance to phages but, as the receptors that the phage use to get into the bacteria are usually based around the bacterial virulence factors, resistant bacteria are likely to be less clinically virulent. Also it is possible (although I’m not sure how much research has been done on this) that at the phages are ‘living’ (or as living as viruses can be) they can evolve with the bacteria, as they do naturally and quite frequently, to attack the resistant bacteria.
Just thought you might find that interesting 🙂
It would be my guess that phage evolve much quicker than bacteria so would be able to cope with bacterial resistance.