[Kurzgesagt] The Deadliest Being on Planet Earth - The Bacteriophage - General

https://youtu.be/YI3tsmFsrOg

Science is fucking awesome

Lol at the Worms reference at 4:41.

Phages are what I imagine self-replicating weaponised nanobots look like. Good to know they're on our side.

Makes me wonder what would happen if say, our use of Bacteriophages eventually lead to them evolving to infect human cells.

Sounds like what some are hoping to use nano machines for, in seeking out and targeting say a specific cancer cell etc. Perhaps bio engineering phages to target cancer cells would work too.

Spread a phage that attacks the bacteria humans need to survive. Bam, evil nanobots are reality.

Since it seems like we're already filled with the things, injecting ones that specifically target things infecting us probably won't make a difference.

little kid me is super disappointed that we still don't have a video game where you play as a an antibody or a bacteriophage.

That's not really going to be a problem since bacteria aren't just in another kingdom, they're an entire domain away from animalia. Viruses are pretty specific things.

So it's like trying to run a Windows virus on Linux you would say?

Kurzgesagt's videos give me so much hope when all news and comments on news are full of negativity.

That Wilhelm scream at 5:11.

Glad I’m not the only one who enjoyed that

Phages are fantastic and I hope the clinical trials succeed, having more tools at our disposal when it comes to disease and infections is important. These endeavors will help save billions and even trillions of lives and also give us the necessary information for us to maybe survive on alien biomes(if we make it that far).

They left out the tidbit that Phages have been commonplace medical practice in eastern Europe/Russia for decades now. There's already a large body of knowledge that can be drawn from, its just getting approval of the FDA and other western medical safety organizations that's lacking. https://www.youtube.com/watch?v=aVTOr7Nq2SM

To be honest, the ending bits with the "Live your life to the fullest!!!" motivational crap often at the end of these videos is the most off-putting part to me

"It turns out that in order to become resistant to even a few species of phages, bacteria have to give up their resistance to antibiotics." That's a big fat [citation needed] right there. Antibiotics operate by a wide variety of mechanisms, and antibiotic resistance mechanisms are equally diverse. They're pretty much independent from resistance mechanisms against bacteriophages, as far as I'm aware. Most of those studies are frankly rubbish. The first large-scale clinical trial for phage therapy ran into a whole bunch of teething problems that pretty much demonstrate why no one has been willing to bring it into the clinic so far. Manufacturing challenges delayed the start of actual trials, and patient recruitment suffered from the specificity of the cocktail they were developing. Their therapy was targeted towards infected burns, but those are often colonised by multiple pathogens and their therapy was only developed for P. aeruginosa and E. coli (which they later dropped as they simply couldn't recruit enough patients with E. coli infections). The trial concluded late last year but the results don't seem to have been released yet. The only reason why we're really bothering with phages now is because highly resistant bacterial infections are becoming increasingly common and phages are a viable method to treat them. Phage therapy is overhyped and I'm not surprised that Kurzgesagt has jumped on the bandwagon just like every other pop sci outlet nowadays.

Ah, that's a shame. I suppose that actual medical evidence in favor for it is just pretty niche in general, beyond that it sounds like anecdotal evidence. Hopefully actual medical precedent can be set so this therapy becomes less overhyped.

So what's the solution to our growing issue with bacteria that aren't susceptible to antibiotics?

New antibiotics, especially ones that work by a novel mechanism. New drugs that disrupt antibiotic resistance mechanisms and allow current antibiotics to work better. Phages are definitely an option and no one is saying that they shouldn't be developed but it's important to know that they aren't the second coming that everyone is making them out to be.

Wouldn't relying on phages mean bacteria simply won't mutate into antibiotic-resistant strains since there's no evolutionary advantage to it, and already-resistant bacteria might lose their resistance since it's not needed?

That actually opens up the worrying thought, what if lazy businesses use pills with both antibiotics and phages at the same time.

The fitness cost of expressing resistance genes is highly variable.[1] Reversion to susceptibility is slow and largely driven by genetic drift[2] and compensatory mutations are far more likely.[3, 4] Relying on phage therapy over antibiotics will subject phages to very strong selection. Given how specific they are, I foresee phage resistance developing much more quickly than antibiotic resistance, putting us right back at square one or worse. Phages will likely be used against infections that have already shown high levels of antibiotic resistance.

But phages are evolving too. Any change that makes a bacteria resistant to a phage would likely still leave the bacteria very, very similar to what the phage was able to infect. Wouldn't it only take a very small change in the phage to be able to infect the bacteria again? If bacteria develop phage resistance quickly, wouldn't phages be able to develop a work-around quickly as well?

It depends on the resistance mechanism; see this review for a short overview of phage resistance mechanisms in bacteria and how phages have evolved to overcome them. While phages do evolve alongside bacteria, phage therapy uses predefined cocktails of phages. This cocktail will need to be updated regularly in order to remain effective. While it may be possible to engineer phages that are more robust to bacterial resistance, it remains to be seen whether this can actually be done, and whether it will work in the clinic.

Without going into phage therapy and how they might be able to keep up through evolution, I'm gonna raise the question how, say, the FDA is gonna handle this kind of treatment. Approval needed for every strain?