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Naive question here: Why can't new antibiotics be developed by just spraying fields of mushrooms or petri dishes full of fungi with antibiotic resistant bacteri

Naive question here: Why can't new antibiotics be developed by just spraying fields of mushrooms or petri dishes full of fungi with antibiotic resistant bacteria and seeing which ones come up with novel ways to fight them?

CarRamrod 2y ago
Birds, mostly
coryrc 2y ago
Because you'll end up finding bacteriophages and wonder why we're wasting so many lives and much money on antibiotics. Antibiotics are lazy. Sure, some people have to die, but at least you didn't have to spend any time taking samples of the actual infection.
- yyyk 2y ago
  Bacteriophages suck. What some people never tell you is that the body treats phages as invaders and can very effectively get rid of them, they are not adapted to the human environment. These are only good for local treatments, sometimes...
  - pazimzadeh 2y ago
    that seems like a good thing. they only infect bacteria, not humans phages are found in large quantities in mucus, where they seemingly contribute to the barrier function of mucus by preying on any bacteria that try go cross https://pubmed.ncbi.nlm.nih.gov/23690590/ https://pubmed.ncbi.nlm.nih.gov/23690590/ https://www.pnas.org/doi/10.1073/pnas.1508355112 https://www.pnas.org/doi/10.1073/pnas.1508355112 https://journals.asm.org/doi/10.1128/mbio.01984-19 https://journals.asm.org/doi/10.1128/mbio.01984-19 this might be adaptable for therapeutics https://www.nature.com/articles/s41467-024-48560-2 https://www.nature.com/articles/s41467-024-48560-2 https://www.nature.com/articles/s42003-024-07269-0 https://www.nature.com/articles/s42003-024-07269-0
  - drob518 2y ago
    Well, you actually want the body to clear things. That’s not a problem, it’s a feature. If the phage is able to target the bacteria before it is fully cleared, that’s all you need. Humans have been injected with phages and it has been shown to work. The Soviets actually did a lot of research on it, IIRC. The practical issue that is really challenging for broad phage therapy adoption is that phages are very specific to the bacteria they target. So, you can’t just get injected with any old phage and expect it to work. Instead, you need to catalog all the phages you find in a database and search for one that can target the specific bacteria the patient has been infected with. Phages are simply viruses that target bacteria. You’re awash in them all the time.
    - yyyk 2y ago
      It's a good thing, unless the body clears off the phage first, leading to both reduced effectiveness and the body wasting immune resources. It does work locally, and one can probably engineer it today to work even better. But it seems to be destined to be relegated to a secondary cure. We seem to be able to keep finding new antibiotics with benefits like 'massive safety testing' or 'we know exactly how they work', or 'very easy to administer'.
    - DeathArrow 2y ago
      >you need to catalog all the phages you find in a database and search for one that can target the specific bacteria the patient has been infected with. Most of the time the doctor doesn't know the exact pathogen you are infected with. He'll suspect a bacterian infection of some kind and prescribe a wide range antibiotic. Doing what you suggest will require changing the way we do medicine. Which might not be a bad thing but requires some determination.
      - nomadpenguin 2y ago
        This is correct, it's called empiric treatment. If a patient comes in with altered mental status and neck rigidity, you don't have time to take a lumbar puncture and culture bacteria. I don't know anything about phage treatment, but from what the other commenter said, it seems like then you'd have to do some sort of PCR test as well. You simply don't have time for any of that -- your only choice is to blast them with vancomycin + ceftriaxone.
- rscho 2y ago
  Thank you so much for volunteering!
  - xialo 2y ago
    Hey @rscho I saw a comment of yours from a few months ago on this site and I want to get a hold of you, I didn't know a better way than replying to your latest comment. Can you message me on discord? username: tag_durden If you have a better contact method let me know i just didnt wanna put my email out here.
    - rscho 2y ago
      I don't use discord. raoul.schorer@gmail.com
- noduerme 2y ago
  Ok, another naive question: Not suggesting we just eat a bunch of bacteriophages, but why wouldn't studying phage mechanisms / proteins for killing bacteria be equally useful?
  - drob518 2y ago
    This is being studied. Phage research is active.
    - coryrc 2y ago
      We need to implement it! Steffanie Strathdee could save her husband's life because she was the director of UC San Diego’s Global Health Institute. "Regular" people deserve to live too. https://www.buzzfeednews.com/article/azeenghorayshi/navy-phage-viruses-for-antibiotics-crisis https://www.buzzfeednews.com/article/azeenghorayshi/navy-pha...
  - kelnos 2y ago
    I'm sure people are studying them. But as GP said, antibiotic are lazy. A doctor would much rather prescribe an antibiotic than do the work to match the specific bacterial infection with the particular phage to deal with it. And since antibiotics still work (for now), there's not all that much money in phage research. If we do get to the point where we "run out" of antibiotics due to bacterial resistance, I imagine phage research will become a lot more attractive as a destination for research funding.
  - coryrc 2y ago
    They're viruses, so they work by infecting bacteria and making the bacteria create more of itself. Antibiotics are found by isolating a compound some i.e. fungi naturally produces. We figure out how to produce the compound and don't fill people with fungi to produce it. Bacteriophages are already the analogy to the compound itself. So we should be investing heavily in creating and distributing all variety of bacteriophage for all our common bacterial infections. 20k deaths/year from MRSA in the USA alone, 120k infections/year in USA and many of the survivors are left with life-long complications.
- drob518 2y ago
  To expand on what you wrote, the challenge with phages is that they’re highly specific to certain bacteria, in the same way that some viruses target gorillas and some target humans. We have yet to find broad spectrum phages. While humans have been saved from bacteria by phages, it requires identifying the bacteria strain, looking up appropriate phage that can target that bacteria, cultivating a dose of the phage, etc. So, yea, phages are highly effective, but there are practical challenges. As you say, antibiotics are lazy.
- mschuster91 2y ago
  The problem is, phages are recognized by your immune system too. They're effectively single-shot, last ditch efforts.
b3lvedere 2y ago
I'm absolutely not educated in the world of antibiotics, but i can imagine it might be very difficult to monitor this kind of complex behaviour in a (hopefuly) very secured controlled environment.
looperhacks 2y ago
Can't answer this particular question. But I remember hearing that developing new antibiotics is not very profitable - To minimize resistance building against new antibiotics, old antibiotics will be used until they are no longer working. So new antibiotics just won't sell that much for now.
- deleted 2y ago
  [deleted]
- xoxosc 2y ago
  Same goes for chemo therapy. There are many chemo therapies from 60s still being used due to the fact their patent is still owned by certain oligarchy.
  - kelnos 2y ago
    > There are many chemo therapies from 60s still being used due to the fact their patent is still owned by certain oligarchy. They must be making some novel improvements, though. Those original patents from the '60s are long expired by now.
    - themaninthedark 2y ago
      They probably are. It's like the claim that pharma had tripled the price of a 100 year old drug(insulin) that the inventors had sold for only $1 and were now charging $450 a month for it. Then you dig into the claims and you find out that, the original insulin is still available, it's new formulations that have the higher cost. >Until now, the only so-called “Walmart insulin” you could get for a lower price (roughly $25 to $35 per vial) was the older, human versions of insulin — R (or Regular) insulin, N (which is Novolin, aka NPH insulin); and a 70/30 mix of the two other types. Those formulations have been around since the early 1980s, but they work much differently and are seen as much less reliable than the analog insulins that first started appearing in the later 1990s. https://www.healthline.com/diabetesmine/walmart-relion-novolog-low-cost-insulin https://www.healthline.com/diabetesmine/walmart-relion-novol... But the new stuff works better, is faster acting and allows a freer lifestyle. I agree that there is a problem with the pharma industry but lying about the problem to try and get change is not going to help the cause.
trentlott 2y ago
It's much easier if you invest in observing the natural world that has had hundreds of millions of years to do the work, without the limitation of human intention.
- nonrandomstring 2y ago
  The Amazon rainforest has evolved for at least 55 million years. It is likely home to millions of compounds of potential medicinal value. In just 50 years 100 million hectares, 390 billion individual trees 16,000 visible species and (estimated unknown) >100,000 types of non-visible fungi, bacterium, microbes etc, have been destroyed. It's why I found this wide-eyed statement in TFA particularly cringe: The discovery shows that "there is terrifically interesting stuff hiding in plain sight".
thegabriele 2y ago
May I suggest you to watch "Common Side Effects" - an very good animated series loosely based on your premises?
- 0xEF 2y ago
  It's a fantastic show, but I am not sure it touches on the commenter's point at all. The show is a take on what might happen if a panacea was actually found to exist. That's a bit different than a mere novel antibiotic. I even think the writers are pulling a lot of punch with how violent and insane Big Pharm, Governments and even independent groups would get about control over it. Still, highly recommend people watch it. Great animation and art style, good writing and characterization, music is pretty rad and it's quite the trip at times.
  - noduerme 2y ago
    I haven't watched the show, but your description just made me think about the "panacea". Virus-wise, I was obsessed with the idea of the DRACO antiviral concept for years.[0] It's really unclear why funding was pulled for it. Then again, the idea behind "28 Days Later" was that everyone got a cancer vaccine and turned into zombies... [0] https://riderinstitute.org/discovery/ https://riderinstitute.org/discovery/
    - adzm 2y ago
      > the idea behind "28 Days Later" was that everyone got a cancer vaccine and turned into zombies This was not in the movie at all. It was the extremely contagious "rage" virus, inadvertently released by animal rights activists.
      - noduerme 2y ago
        Oops. I got mixed up. I was thinking of the virus designed to cure cancer in "I Am Legend."
hawkjo 2y ago
Producing large quantities of drug resistant bacteria sounds at least BSL3. The principle might make sense, but one wouldn’t “spray the fields” of something like that.
throw310822 2y ago
Or try an evolutionary approach. Artificially enforce some dependency between an organisms' (fungi, bacteria) ability to kill a wide spectrum of targets, and their own continued survival. Let the organism spread on a large matrix in close contact with the targets and zap the areas where the targets are thriving; repeat until you have evolved strains that are effective in destroying the targets. Wonder if it's possible or even been tried.
- treyd 2y ago
  I believe there's a group [1] at the MIT Media Lab doing this. Certainly others. [1] https://www.media.mit.edu/groups/sculpting-evolution/overview/ https://www.media.mit.edu/groups/sculpting-evolution/overvie...
bluGill 2y ago
What makes you think there exists a way to fight that isn't harmful the host. Antibiotics work by stopping some biologicial pathway - there are only so many of those in bacteria, you can stop them at any point of course, but you have to stop it. However most of those pathways are also in other lifeforms and so stopping the pathway means you kill not only the bacteria but also human/mushroom. We have been lucky that we have found a few pathways that are not in human (read mammals) that are in bacteria we worry about. However bacteria just finds a different pathway and odds are that is a pathway in humans and so we can't use it because it would kill humans as well.

CarRamrod 2y ago

Birds, mostly

coryrc 2y ago

Because you'll end up finding bacteriophages and wonder why we're wasting so many lives and much money on antibiotics. Antibiotics are lazy. Sure, some people have to die, but at least you didn't have to spend any time taking samples of the actual infection.

yyyk 2y ago
Bacteriophages suck. What some people never tell you is that the body treats phages as invaders and can very effectively get rid of them, they are not adapted to the human environment. These are only good for local treatments, sometimes...
- pazimzadeh 2y ago
  that seems like a good thing. they only infect bacteria, not humans phages are found in large quantities in mucus, where they seemingly contribute to the barrier function of mucus by preying on any bacteria that try go cross https://pubmed.ncbi.nlm.nih.gov/23690590/ https://pubmed.ncbi.nlm.nih.gov/23690590/ https://www.pnas.org/doi/10.1073/pnas.1508355112 https://www.pnas.org/doi/10.1073/pnas.1508355112 https://journals.asm.org/doi/10.1128/mbio.01984-19 https://journals.asm.org/doi/10.1128/mbio.01984-19 this might be adaptable for therapeutics https://www.nature.com/articles/s41467-024-48560-2 https://www.nature.com/articles/s41467-024-48560-2 https://www.nature.com/articles/s42003-024-07269-0 https://www.nature.com/articles/s42003-024-07269-0
- drob518 2y ago
  Well, you actually want the body to clear things. That’s not a problem, it’s a feature. If the phage is able to target the bacteria before it is fully cleared, that’s all you need. Humans have been injected with phages and it has been shown to work. The Soviets actually did a lot of research on it, IIRC. The practical issue that is really challenging for broad phage therapy adoption is that phages are very specific to the bacteria they target. So, you can’t just get injected with any old phage and expect it to work. Instead, you need to catalog all the phages you find in a database and search for one that can target the specific bacteria the patient has been infected with. Phages are simply viruses that target bacteria. You’re awash in them all the time.
  - yyyk 2y ago
    It's a good thing, unless the body clears off the phage first, leading to both reduced effectiveness and the body wasting immune resources. It does work locally, and one can probably engineer it today to work even better. But it seems to be destined to be relegated to a secondary cure. We seem to be able to keep finding new antibiotics with benefits like 'massive safety testing' or 'we know exactly how they work', or 'very easy to administer'.
  - DeathArrow 2y ago
    >you need to catalog all the phages you find in a database and search for one that can target the specific bacteria the patient has been infected with. Most of the time the doctor doesn't know the exact pathogen you are infected with. He'll suspect a bacterian infection of some kind and prescribe a wide range antibiotic. Doing what you suggest will require changing the way we do medicine. Which might not be a bad thing but requires some determination.
    - nomadpenguin 2y ago
      This is correct, it's called empiric treatment. If a patient comes in with altered mental status and neck rigidity, you don't have time to take a lumbar puncture and culture bacteria. I don't know anything about phage treatment, but from what the other commenter said, it seems like then you'd have to do some sort of PCR test as well. You simply don't have time for any of that -- your only choice is to blast them with vancomycin + ceftriaxone.
rscho 2y ago
Thank you so much for volunteering!
- xialo 2y ago
  Hey @rscho I saw a comment of yours from a few months ago on this site and I want to get a hold of you, I didn't know a better way than replying to your latest comment. Can you message me on discord? username: tag_durden If you have a better contact method let me know i just didnt wanna put my email out here.
  - rscho 2y ago
    I don't use discord. raoul.schorer@gmail.com
noduerme 2y ago
Ok, another naive question: Not suggesting we just eat a bunch of bacteriophages, but why wouldn't studying phage mechanisms / proteins for killing bacteria be equally useful?
- drob518 2y ago
  This is being studied. Phage research is active.
  - coryrc 2y ago
    We need to implement it! Steffanie Strathdee could save her husband's life because she was the director of UC San Diego’s Global Health Institute. "Regular" people deserve to live too. https://www.buzzfeednews.com/article/azeenghorayshi/navy-phage-viruses-for-antibiotics-crisis https://www.buzzfeednews.com/article/azeenghorayshi/navy-pha...
- kelnos 2y ago
  I'm sure people are studying them. But as GP said, antibiotic are lazy. A doctor would much rather prescribe an antibiotic than do the work to match the specific bacterial infection with the particular phage to deal with it. And since antibiotics still work (for now), there's not all that much money in phage research. If we do get to the point where we "run out" of antibiotics due to bacterial resistance, I imagine phage research will become a lot more attractive as a destination for research funding.
- coryrc 2y ago
  They're viruses, so they work by infecting bacteria and making the bacteria create more of itself. Antibiotics are found by isolating a compound some i.e. fungi naturally produces. We figure out how to produce the compound and don't fill people with fungi to produce it. Bacteriophages are already the analogy to the compound itself. So we should be investing heavily in creating and distributing all variety of bacteriophage for all our common bacterial infections. 20k deaths/year from MRSA in the USA alone, 120k infections/year in USA and many of the survivors are left with life-long complications.
drob518 2y ago
To expand on what you wrote, the challenge with phages is that they’re highly specific to certain bacteria, in the same way that some viruses target gorillas and some target humans. We have yet to find broad spectrum phages. While humans have been saved from bacteria by phages, it requires identifying the bacteria strain, looking up appropriate phage that can target that bacteria, cultivating a dose of the phage, etc. So, yea, phages are highly effective, but there are practical challenges. As you say, antibiotics are lazy.
mschuster91 2y ago
The problem is, phages are recognized by your immune system too. They're effectively single-shot, last ditch efforts.

b3lvedere 2y ago

I'm absolutely not educated in the world of antibiotics, but i can imagine it might be very difficult to monitor this kind of complex behaviour in a (hopefuly) very secured controlled environment.

looperhacks 2y ago

Can't answer this particular question. But I remember hearing that developing new antibiotics is not very profitable - To minimize resistance building against new antibiotics, old antibiotics will be used until they are no longer working. So new antibiotics just won't sell that much for now.

deleted 2y ago
[deleted]
xoxosc 2y ago
Same goes for chemo therapy. There are many chemo therapies from 60s still being used due to the fact their patent is still owned by certain oligarchy.
- kelnos 2y ago
  > There are many chemo therapies from 60s still being used due to the fact their patent is still owned by certain oligarchy. They must be making some novel improvements, though. Those original patents from the '60s are long expired by now.
  - themaninthedark 2y ago
    They probably are. It's like the claim that pharma had tripled the price of a 100 year old drug(insulin) that the inventors had sold for only $1 and were now charging $450 a month for it. Then you dig into the claims and you find out that, the original insulin is still available, it's new formulations that have the higher cost. >Until now, the only so-called “Walmart insulin” you could get for a lower price (roughly $25 to $35 per vial) was the older, human versions of insulin — R (or Regular) insulin, N (which is Novolin, aka NPH insulin); and a 70/30 mix of the two other types. Those formulations have been around since the early 1980s, but they work much differently and are seen as much less reliable than the analog insulins that first started appearing in the later 1990s. https://www.healthline.com/diabetesmine/walmart-relion-novolog-low-cost-insulin https://www.healthline.com/diabetesmine/walmart-relion-novol... But the new stuff works better, is faster acting and allows a freer lifestyle. I agree that there is a problem with the pharma industry but lying about the problem to try and get change is not going to help the cause.

trentlott 2y ago

It's much easier if you invest in observing the natural world that has had hundreds of millions of years to do the work, without the limitation of human intention.

nonrandomstring 2y ago
The Amazon rainforest has evolved for at least 55 million years. It is likely home to millions of compounds of potential medicinal value. In just 50 years 100 million hectares, 390 billion individual trees 16,000 visible species and (estimated unknown) >100,000 types of non-visible fungi, bacterium, microbes etc, have been destroyed. It's why I found this wide-eyed statement in TFA particularly cringe: The discovery shows that "there is terrifically interesting stuff hiding in plain sight".

thegabriele 2y ago

May I suggest you to watch "Common Side Effects" - an very good animated series loosely based on your premises?

0xEF 2y ago
It's a fantastic show, but I am not sure it touches on the commenter's point at all. The show is a take on what might happen if a panacea was actually found to exist. That's a bit different than a mere novel antibiotic. I even think the writers are pulling a lot of punch with how violent and insane Big Pharm, Governments and even independent groups would get about control over it. Still, highly recommend people watch it. Great animation and art style, good writing and characterization, music is pretty rad and it's quite the trip at times.
- noduerme 2y ago
  I haven't watched the show, but your description just made me think about the "panacea". Virus-wise, I was obsessed with the idea of the DRACO antiviral concept for years.[0] It's really unclear why funding was pulled for it. Then again, the idea behind "28 Days Later" was that everyone got a cancer vaccine and turned into zombies... [0] https://riderinstitute.org/discovery/ https://riderinstitute.org/discovery/
  - adzm 2y ago
    > the idea behind "28 Days Later" was that everyone got a cancer vaccine and turned into zombies This was not in the movie at all. It was the extremely contagious "rage" virus, inadvertently released by animal rights activists.
    - noduerme 2y ago
      Oops. I got mixed up. I was thinking of the virus designed to cure cancer in "I Am Legend."

hawkjo 2y ago

Producing large quantities of drug resistant bacteria sounds at least BSL3. The principle might make sense, but one wouldn’t “spray the fields” of something like that.

throw310822 2y ago

Or try an evolutionary approach. Artificially enforce some dependency between an organisms' (fungi, bacteria) ability to kill a wide spectrum of targets, and their own continued survival. Let the organism spread on a large matrix in close contact with the targets and zap the areas where the targets are thriving; repeat until you have evolved strains that are effective in destroying the targets. Wonder if it's possible or even been tried.

treyd 2y ago
I believe there's a group [1] at the MIT Media Lab doing this. Certainly others. [1] https://www.media.mit.edu/groups/sculpting-evolution/overview/ https://www.media.mit.edu/groups/sculpting-evolution/overvie...

bluGill 2y ago

What makes you think there exists a way to fight that isn't harmful the host. Antibiotics work by stopping some biologicial pathway - there are only so many of those in bacteria, you can stop them at any point of course, but you have to stop it. However most of those pathways are also in other lifeforms and so stopping the pathway means you kill not only the bacteria but also human/mushroom. We have been lucky that we have found a few pathways that are not in human (read mammals) that are in bacteria we worry about. However bacteria just finds a different pathway and odds are that is a pathway in humans and so we can't use it because it would kill humans as well.