Okay, no big shock to any of you– bacteria are becoming resistant to our antibiotics. One of the many enteric bacteria (cause kids to poop to death), E. coli, is racking up antibiotic resistance genes like theyre McDonalds Beanie Babies.
What the hell are we going to do?
Bacteriophage are viruses that eat bacteria… lol… Bring in the gators to eat the snakes.
For a long time it was ignored as an option in the US (eh, Soviet medicine). It doesnt help that the Soviet ‘science’ behind phage therapy is murky– yeah, they have commercially available phage therapies, but virtually nothing published about the details of the clinical trials/bacteria/viruses behind them.
But our antibiotic options are dwindling. We need something different, even if its only for very specific infections (O127:K63 E. coli), or very specific diseases (bacterial meningitis), or even if we can only approve of its use in animals, not humans. The real science has started:
So Denou et al have made a realistic list of potential problems of using phage therapy, and have tried to address those problems in their experiments.
1– If you are feeding people bacteriophages to get rid of pathogenic bacteria, how do you know that the viruses wont kill off all your commensal bacteria too?
One of the problems/good things about phages is that they are super-specific for a particular bacteria. The problem side of it, is that if you feed a sick person the wrong phage, nothing will happen to the pathogenic bacteria. Which means you need to culture someones poo before you know what to treat them with. Antibiotics have broad effects– you can treat immediately. Phage, youd have to wait a couple of days, and you might not have that kind of time. Happily, it turns out that you could conceivably make a phage mix’, and youd be sure of catching a majority of potential enteric bacteria for a fast hit. But what are the side effects of this?
They fed healthy mice specific phages, or a cocktail of phages, and cultured their poo — same kinds of normal bacteria in virus(+) as virus(-) mice. Contrast that to the healthy mice that got regular antibiotics, whose normal flora was ravaged.
Phage therapy actually looked better for your normal flora than traditional antibiotics!
2– Okay, feeding people viruses. That means the viruses have to survive the stomach before they get to their targets in the intestines. Hows that going to work?
Denou went back to their healthy mice, gave em some phage, and dissected their digestive system to see where the virus ended up. Yeah… not a whole hell of a lot survived the stomach. There was hardly anything in the intestines, where you want the phage to work.
When they fed viruses to mice infected with bacteria, there was 10-1000 fold more virus where you want it (there are some limitations to this particular experiment, small mouse models of enteric bacteria suck, which actually means the effect is probably greater in humans). This is because phage therapy would be a self-amplifying ‘drug’! Even if just one phage survives the stomach and latches on to a pathogenic bacteria in the intestines, that one infection will result in thousands of more viruses!
3– What are the side effects?
I never take antibiotics. Its not because Im a virologist and I know antibiotics wont do anything to my viral sniffles. Im not allergic to them. Its not because Im, like, totally natural and GMO free and dont want to contaminate mah bodeh with toxic pharmaceuticals.
Antibiotics make me puke. Whenever I like, really need antibiotics, I have to have them injected. Otherwise, I take a pill, and 30 minutes later Im puking. Violently. For hours. Yeah…
Would phages be any better? Well, in this paper they were! Denou fed normal, healthy mice a ton of phage. A ton. They put it in their water at 109 infectious viruses/ml. The mice that got phage in their water developed at the same rate, had the same weight, same behaviors, as the mice that got plain water. Nothing kooky happened. No puking or poopy mice. Even though phage therapy for anything is probably decades away, this result alone is enough to get me excited.
4– Well, youve mentioned before that pathogenic bacteria got their tricks from phages. How do you know phage therapy wont just spread virulence factors and make things worse?
Easy! Pick phages for the cocktail that dont have any known virulence factors! Dont have em, cant spread em. You also need to take other phage-factors into account when picking out which ones are putative therapies– You know how some human viruses are hit-and-run (influenza), and some are hit-and-stick (herpes)? Phages are the same way. Some infect bacteria, go latent, and dont wake up for a million years (phage DNA is inserted into the bacterias genome, kinda like our ERVs!). Some phages infect and immediately go lytic, making lots of babies and blowing up their host cell. The latter are the ones we want in our mix.
Phage therapy might just be a viable solution to some of our antibiotic-resistant problems!