5 ms·

Given the antibiotic stagnation, could we possibly develop something similar to target bacteria? Aka inject instructions in their genome to self destroy?

SketchySeaBeast 6y ago
I wonder if that won't work as well given that we're not using this to cure COVID while we are currently sick with it. I don't know if Syphilis booster shots would make sense or if the range of things we could need to be regularly inoculated for would be far too broad for this to be useful.
passivate 6y ago
Even if you could do that, you'd only kill a handful of bacteria. The mRNA platform doesn't contain genetic code to recreate and repackage itself.
- mmastrac 6y ago
  Obviously not a biologist, but if you could target a specific protein on the bacterial surface it might work. Alternatively you could CRISPR some human cells that generate the bacteria-killing RNA constantly.
  - passivate 6y ago
    Yes, that would be super cool. But also crazy-risky!! :) But the risk is not due to chance, its due to the unknowns. Once they're no longer unknowns we'll be able to engineer such a therapy. Alternatively, once we understand our biology so well, we might as well just patch all the "bugs" so that we don't get infected by harmful pathogens. Or maybe forsake our biology and move on to Silicon ?
- bpodgursky 6y ago
  Neither do standard antibiotics.
  - epmaybe 6y ago
    I assume you’re suggesting that phage therapy would require more than a single dose, similar to antibiotic regimens?
  - passivate 6y ago
    Not sure what your point is. If you want to inject genetic material inside an organism to destroy one cell - with the mRNA platform you can only do it once. It won't repackage itself and 'infect' another cell. If you want to make conditions inhospitable for an organism, you can cause a mass-scale change that affects multiple cells via a drug.
Valgrim 6y ago
The whole concept of phage therapy is somehow based on this: Bacteriophages inject DNA into specific bacteria that makes them copy the phage inside them until they burst open. Basically use viruses against bacteria. https://www.youtube.com/watch?v=YI3tsmFsrOg https://www.youtube.com/watch?v=YI3tsmFsrOg
- searine 6y ago
  The issue with phage therapy is that it has to be targeted. With antibiotics, they are very broad spectrum so you can throw augmentin at routine infections and it'll usually work. With phages, you have to be much more specific. Phage X for bacteria Y. It's not necessarily hard figure out what bacteria it is, but it takes time and expensive lab work.
  - RcouF1uZ4gsC 6y ago
    > It's not necessarily hard figure out what bacteria it is, but it takes time and expensive lab work. Also you may not have time. If the person has meningitis for example, if you wait to try to figure out what bacteria they have before treating, they will be dead. Broad spectrum antibiotics are great for this kind of thing in that you can start treatment immediately, and once you figure out the bacteria, narrow the treatment to that type of bacteria.
  - suifbwish 6y ago
    This is also why bacteria can develop resistance to antibiotics. You can’t develop resistance against something that is 99.999% effective through design
    - dnautics 6y ago
      it's not like bacteria haven't developed resistance to phages. what do you think CRISPR is?
      - Fomite 6y ago
        Interestingly, in several phage-treated patients, the bacteria then had increased susceptibility to antibiotics. Combination therapy is a remarkable thing.
Lichtso 6y ago
https://en.wikipedia.org/wiki/Phage_therapy https://en.wikipedia.org/wiki/Phage_therapy
Protostome 6y ago
In addition to phage therapy option mentioned here, there's also a class of synthetic polymers that selectively disrupts only bacterial DNA. Those molecules can't cross the nucleus and therefore are not toxic to eucaryotes. This therapeutic direction has two key advantages over other approaches: 1. There's no way bacteria can develop resistance to it in the next 1b years, since those synthetic polymers bind to free DNA without any preference to particular sequences. Therefore, there's no known mechanism (mutations, horizontal gene transfer, etc) that can provide immunity against this class of agents. 2. Being a "small" molecule it has much less risk of eliciting an immune response ( unlike phages, who may invoke some response from immune cells which can decrease the potency of the treatment) Here is the latest study i'm familiar with that showed pretty good results in animal models: https://pubmed.ncbi.nlm.nih.gov/33571116/ https://pubmed.ncbi.nlm.nih.gov/33571116/
- petertodd 6y ago
  > and therefore are not toxic to eucaryotes. Not toxic directly. Disrupting "good" bacteria that we co-exist with isn't always harm free, as I'm sure the people researching those polymers are well aware of.
  - Fomite 6y ago
    See: C. difficle infections
  - Protostome 6y ago
    That is correct, the same problem exist for current antibiotics which are generally considered safe
- colordrops 6y ago
  Regarding 1, a bacteria could evolve a cell surface that blocks the polymer in the same way a eukaryotic nucleus does.
  - Protostome 6y ago
    That is possible, but we're talking about different time constants here. Antibiotic resistance can arise in a few generations. Evolving a different membrane composition that will block that particular toxin and not the other ingredients the cell requires to function (amino acids, carbohydrates, etc), is much less probable to take place in such a short time

SketchySeaBeast 6y ago

I wonder if that won't work as well given that we're not using this to cure COVID while we are currently sick with it. I don't know if Syphilis booster shots would make sense or if the range of things we could need to be regularly inoculated for would be far too broad for this to be useful.

passivate 6y ago

Even if you could do that, you'd only kill a handful of bacteria. The mRNA platform doesn't contain genetic code to recreate and repackage itself.

mmastrac 6y ago
Obviously not a biologist, but if you could target a specific protein on the bacterial surface it might work. Alternatively you could CRISPR some human cells that generate the bacteria-killing RNA constantly.
- passivate 6y ago
  Yes, that would be super cool. But also crazy-risky!! :) But the risk is not due to chance, its due to the unknowns. Once they're no longer unknowns we'll be able to engineer such a therapy. Alternatively, once we understand our biology so well, we might as well just patch all the "bugs" so that we don't get infected by harmful pathogens. Or maybe forsake our biology and move on to Silicon ?
bpodgursky 6y ago
Neither do standard antibiotics.
- epmaybe 6y ago
  I assume you’re suggesting that phage therapy would require more than a single dose, similar to antibiotic regimens?
- passivate 6y ago
  Not sure what your point is. If you want to inject genetic material inside an organism to destroy one cell - with the mRNA platform you can only do it once. It won't repackage itself and 'infect' another cell. If you want to make conditions inhospitable for an organism, you can cause a mass-scale change that affects multiple cells via a drug.

Valgrim 6y ago

The whole concept of phage therapy is somehow based on this: Bacteriophages inject DNA into specific bacteria that makes them copy the phage inside them until they burst open. Basically use viruses against bacteria. https://www.youtube.com/watch?v=YI3tsmFsrOg https://www.youtube.com/watch?v=YI3tsmFsrOg

searine 6y ago
The issue with phage therapy is that it has to be targeted. With antibiotics, they are very broad spectrum so you can throw augmentin at routine infections and it'll usually work. With phages, you have to be much more specific. Phage X for bacteria Y. It's not necessarily hard figure out what bacteria it is, but it takes time and expensive lab work.
- RcouF1uZ4gsC 6y ago
  > It's not necessarily hard figure out what bacteria it is, but it takes time and expensive lab work. Also you may not have time. If the person has meningitis for example, if you wait to try to figure out what bacteria they have before treating, they will be dead. Broad spectrum antibiotics are great for this kind of thing in that you can start treatment immediately, and once you figure out the bacteria, narrow the treatment to that type of bacteria.
- suifbwish 6y ago
  This is also why bacteria can develop resistance to antibiotics. You can’t develop resistance against something that is 99.999% effective through design
  - dnautics 6y ago
    it's not like bacteria haven't developed resistance to phages. what do you think CRISPR is?
    - Fomite 6y ago
      Interestingly, in several phage-treated patients, the bacteria then had increased susceptibility to antibiotics. Combination therapy is a remarkable thing.

Lichtso 6y ago

https://en.wikipedia.org/wiki/Phage_therapy https://en.wikipedia.org/wiki/Phage_therapy

Protostome 6y ago

In addition to phage therapy option mentioned here, there's also a class of synthetic polymers that selectively disrupts only bacterial DNA. Those molecules can't cross the nucleus and therefore are not toxic to eucaryotes. This therapeutic direction has two key advantages over other approaches: 1. There's no way bacteria can develop resistance to it in the next 1b years, since those synthetic polymers bind to free DNA without any preference to particular sequences. Therefore, there's no known mechanism (mutations, horizontal gene transfer, etc) that can provide immunity against this class of agents. 2. Being a "small" molecule it has much less risk of eliciting an immune response ( unlike phages, who may invoke some response from immune cells which can decrease the potency of the treatment) Here is the latest study i'm familiar with that showed pretty good results in animal models: https://pubmed.ncbi.nlm.nih.gov/33571116/ https://pubmed.ncbi.nlm.nih.gov/33571116/

petertodd 6y ago
> and therefore are not toxic to eucaryotes. Not toxic directly. Disrupting "good" bacteria that we co-exist with isn't always harm free, as I'm sure the people researching those polymers are well aware of.
- Fomite 6y ago
  See: C. difficle infections
- Protostome 6y ago
  That is correct, the same problem exist for current antibiotics which are generally considered safe
colordrops 6y ago
Regarding 1, a bacteria could evolve a cell surface that blocks the polymer in the same way a eukaryotic nucleus does.
- Protostome 6y ago
  That is possible, but we're talking about different time constants here. Antibiotic resistance can arise in a few generations. Evolving a different membrane composition that will block that particular toxin and not the other ingredients the cell requires to function (amino acids, carbohydrates, etc), is much less probable to take place in such a short time