Will phages replace the use of failing antibiotics

[Jet Cash]

There seems to be a revival in the interest in bacteriophage following the increasing ineffectiveness of antibiotics. This should improve world health, and reduce the profits of the Big Pharma companies. Hopefully we will start to see an increase in their use fairly soon. They were discovered in 1919, but were sidelined for apparent political reasons. There are quite a few videos around, but this one gives a brief intro to their history.

https://www.youtube.com/watch?v=32DAiICOxoM

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[Jet Cash]

I'm encouraged. There are several videos and comments about this that are starting to appear, and I understand that the government has started to research this with the objective of adding treatment to the health system. Hopefully they will keep this away from big pharma.

[The Sceptical Chymist]

I took an elective course in virology back in 1999, and though I don't remember much from it, I do recall the structure of bacteriophages.  Their capsid looks like an alien spaceship with legs if I recall correctly.  Haven't watched the video yet.

Interesting concept, though I wonder how safe it is using a virus to kill bacteria.  Viruses do mutate, and I would think it'd be possible that a phage could somehow infect human cells given enough time.  That's my initial thought, but I'm no expert in viruses.

Why do you think big pharma wouldn't profit from this?  If indeed phages started to get used as medicine, someone would have to manufacture and distribute them to pharmacies and so forth.  I'd say it would actually be a big opportunity for them--but again, I haven't yet watched that video or read anything about this.  I'll look into it some and perhaps edit this post.

[Jet Cash]

I need to do some more reading, and I'm not sure how they would introduce cultured phages into the body. It seems that we already have millions in us, and they rush to protect an open wound, but those would be "natural" phages. I understand that they need to match phages to specific bacterial types.

How would Big Pharma be able to keep alive batches of phages to provide a stock for treatment?

[The Sceptical Chymist]

How would Big Pharma be able to keep alive batches of phages to provide a stock for treatment?

Viruses aren't "alive".  They're just some genetic material surrounded by a protein coat.  They don't have organelles like cells do; they don't metabolize energy sources; and they can't reproduce outside of a host.  They basically hijack a cell's machinery to make more viruses. 

And I have no idea how you'd make a useful product out of a bacteriophage.  I do know that an entire field of pharmcology is devoted to drug delivery systems (pharmaceutics), and they've come up with some pretty incredible stuff like extended-release drugs and that kind of thing.  I had a friend who got his PhD in pharmaceutics, and he was working on liposomal delivery of some kind of DNA-based thing.  It's tough, because your body tries to get rid of anything foreign that it can't use. 

Ever wonder why you can't take insulin or a vaccine orally?  Ever wonder why there haven't been gene therapies yet?  That's all part of what they work on, and I would think that pharmaceutical science might be able to figure out how to use phages for infections, assuming they're useful and safe.  Bacteria are figuring out ways to get past most antibiotics, and it's just a matter of time before they're resistant to everything on the market.  If we don't start cranking out new classes of antibiotics, we're screwed.  Superbugs are going to emerge eventually which nothing will be able to treat.  That might not happen in my lifetime, but it *could* happen.

[actmyname]

Would it be possible to introduce a population of bacteria that are not as resistant to antibiotics in order to increase the competition of resources in the space?

The key point would be to keep them around long enough to start having a drift towards non-superbugs but not enough to induce dangerous health conditions. If you had a resource-heavy bacterium that was not dangerous to humans, it might do some good.

I'm no biologist, though, so feel free to blast this idea out of the water.Waiting on CRISPR.

[o_e_l_e_o]

Would it be possible to introduce a population of bacteria that are not as resistant to antibiotics in order to increase the competition of resources in the space?

I'm sure I read about something like this years ago, and I have, on occasion, tried to search for a source, but I've never been able to find one. I have a feeling it was a chapter in a book rather than an article or a paper. If anyone knows, please direct it my way. It's an interesting idea, and it wouldn't even require the introduction of a new population as this population already exists.

The hypothesis, very basically, goes along these lines:

You have a wild population of bacteria, say, Staphylococcus aureus. To this population, you introduce a penicillin based antibiotic. Now, this penicillin antibiotic might wipe out the majority of these bacteria, but there will be a few which are resistant to it due to various random genetic mutations. There are various ways for a bacterium to be resistant to an antibiotic - it can produce an enzyme which breaks down the antibiotic, it can develop a new metabolic pathway to bypass the one affected by the antibiotic, it can actively pump the antibiotic out of itself, it can alter the receptor or protein which the antibiotic binds to, etc. In the case of S. aureus and penicillins, it is the last of these.

Now, this altered protein, while being more resistant to the effects of the antibiotic, is less effective and efficient than the non-resistant wild type. The evolutionary selection pressure for the the last however many millions of years and trillions of generations has been efficiency, and so the wild type protein is hugely efficient. Now, however, you have changed the selection pressure to be that of penicillin resistance. The less efficient but more resistant protein is now favored. Because it is less efficient, the cell has to spend more energy to produce it, and dedicate more of its resources to using it. Over time, with the ongoing penicillin resistant selection pressure, the protein evolves to become even better at withstanding penicillin, but at further cost to its overall efficiency.

If we removed the selection pressure of the antibiotic, then the wild type once again becomes the favored protein - it is more efficient in the absence of the antibiotic, after all. Over time the wild type bacteria, which is more energy efficient, would out compete the penicillin resistant bacteria for resources, as the penicillin resistant population is spending additional energy and resources on manufacturing a sub-optimal protein. The resistant population would essentially be out-bred to near extinction by the wild type population.

This has been proven in a lab setting - a wild type population will out compete an antibiotic resistant population in the absence of the antibiotic, as the resistant population has to spend additional energy and resources on its now unnecessary resistance. If we could completely ban penicillins from being used in every country around the world for a number of years, the hypothesis is that penicillin resistance would more-or-less disappear, and they would again become the wonder drug that they were back in the 40s and 50s. The problem being that this is essentially unworkable on a global scale. With the ubiquitousness of international travel, a single surviving population of penicillin resistant organisms would rapidly move around the world and recolonise areas where they had previously been eradicated.

[actmyname]

-snip-

Consideration:

Artificial selection of high resource-consuming bacteria.
Further artificial selection can be made to ensure that they are: quickly-reproducing, inert, cannibalistic (e.g. B. subtilis) or a combination thereof.

Keep them grown in isolated environments and release them in large doses. They may die out but they will take the less-inert bacteria with them. That is the key point: rather than natural selection now favoring antibiotic-resistant bacteria, it is now favoring bacteria that take less resources, whether antibiotic-resistant or not.

It might be a double-edged sword, though, if the residual bacteria population starts mingling with that of surviving antibiotic-resistant populations.

[o_e_l_e_o]

Further artificial selection can be made to ensure that they are: quickly-reproducing, inert, cannibalistic (e.g. B. subtilis) or a combination thereof.

Possible, but very risky.

Horizontal gene transfer occurs between populations of bacteria. By this, we mean the transferring of DNA or other genetic information between two "adult" cells, as opposed to the usual parent-to-child transferring of DNA we are all familiar with. This is largely the mechanism by how antibiotic resistance conferring genes spread among bacteria, and it is not limited to bacteria of the same species.

Introducing a population of genetical modified bacteria as you suggest could result in a variety of undesirable outcomes. The "quickly-reproducing" gene could be transferred to the antibiotic resistant population, resulting in an even worse superbug which can now outcompete and outgrow all other bacteria. Through normal evolutionary mutations, the "inert" gene could become deactivated, and your genetically modified bacteria suddenly become pathogenic. You also run the risk of out competing all bacteria, including the so called "good" commensal and mutualistic bacteria, leaving little competition for the few surviving antibiotic resistant bacteria, which can then multiply even more rapidly.

I'm sure a microbiologist could offer more "known unknown" worst case scenarios. There is also, of course, the "unknown unknowns".

[paxmao]

Viruses aren't "alive".  ...

Oh well, that is a bit controversial. It is true that the definition of a living creature is one that is born, develops, multiplies and dies. Virus can´t multiply by themselves, however neither can many parasites and they are considered living creatures.

[paxmao]

Would it be possible to introduce a population of bacteria that are not as resistant to antibiotics in order to increase the competition of resources in the space?

Ask the Australians how did that went. They introduced mixomatosis to kill the rabits in the 50s, 10 percent developed immunity and now they had to introduce another illness to control that (calcinoma). There are as many bacteria in a few spoons of water as rabits in australia.

 AFAIK, every time man has tried to modify an ecosystem by inserting a "favourable" species has created more trouble than anything else.

[actmyname]

Oh well, that is a bit controversial. It is true that the definition of a living creature is one that is born, develops, multiplies and dies. Virus can´t multiply by themselves, however neither can many parasites and they are considered living creatures.

It's just the technicality of it. Parasites should be able to reproduce genetically on their own. They just rely on nutrition from other organisms.

Viruses are no more alive than Von Neumann probes.

[Farul]

There seems to be a revival in the interest in bacteriophage following the increasing ineffectiveness of antibiotics. This should improve world health, and reduce the profits of the Big Pharma companies. Hopefully we will start to see an increase in their use fairly soon. They were discovered in 1919, but were sidelined for apparent political reasons. There are quite a few videos around, but this one gives a brief intro to their history.

https://www.youtube.com/watch?v=32DAiICOxoM

There Is A Video About The Pros And Cons Of Bacteriophage Compared To Antibiotics
https://www.youtube.com/watch?v=YI3tsmFsrOg
(If You Need Citation Maybe You Can Ask At r/kurzgesagt)

Phages Only Kill Certain Type Of Bacteria, You Need A Certain Type Of Phages To Cure A Disease.
For Example [X] Phages Can Only Kill [X] Type Of Bacteria, It Can't Kill [Y] Bacteria.
Unlike Antibiotics That Can Kill Almost All Type Of Bacteria, Therefore, They Also Can Easily Mass Produced.

BTW Phages Actually Already Used In Some Ex-Soviet Countries.
It Maybe Because In The Soviet Era, The Soviet Heavily Invested On Phages^[1]
It Maybe Because The Soviet Can't Access To Western Antibiotics, Or Just Because They're COMMUNIST

[paxmao]

Oh well, that is a bit controversial. .

It's just the technicality of it. Parasites should be able to reproduce genetically on their own. They just rely on nutrition from other organisms.

Viruses are no more alive than Von Neumann probes.

See ? Controversial

[DaveF]

Phages Only Kill Certain Type Of Bacteria, You Need A Certain Type Of Phages To Cure A Disease.
For Example [X] Phages Can Only Kill [X] Type Of Bacteria, It Can't Kill [Y] Bacteria.
Unlike Antibiotics That Can Kill Almost All Type Of Bacteria, Therefore, They Also Can Easily Mass Produced.

Which is the big problem with phages.
You have a head cold, you ignore it. You develop a sinus infection.
Last year there were 5 or 6 (could be more don't remember) different strains of bacteria causing sinus infections. (yeah I got 2 different ones, lucky me)
1 broad spectrum antibiotic worked on both of mine (and most of the other ones too). Doing it with phages requires a culture to determine which one(s) you need.
-Dave

[aplistir]

There seems to be a revival in the interest in bacteriophage following the increasing ineffectiveness of antibiotics. This should improve world health, and reduce the profits of the Big Pharma companies. Hopefully we will start to see an increase in their use fairly soon. They were discovered in 1919, but were sidelined for apparent political reasons. There are quite a few videos around, but this one gives a brief intro to their history.

I think new antibiotics will replace old antibiotics Not phages. Phages are good, but each phage work against just one type of bacteria. So you would need lots of different kinds of them...

I read an article about new antibiotics, which if they get approved would solve our problems. Some of them were predicted that bacteria's couldn't ever build resistance against. (Yep. Ever is a long time)
 
If I recall correctly the problem with those were that they were even TOO effective.

Sorry, I don't have a link to the article, but searching with words: "new soil antibiotics resistance" should give some interesting results.

Phages Only Kill Certain Type Of Bacteria, You Need A Certain Type Of Phages To Cure A Disease.

Which is the big problem with phages.
1 broad spectrum antibiotic worked on both of mine (and most of the other ones too). Doing it with phages requires a culture to determine which one(s) you need.
-Dave

It is a problem, but also a good thing. With phages you have no side effects, because they only attack the infection causing bacteria and nothing else.