5 ms·

One of the major critiques of phage therapy is that it will fail the same way antibiotics have failed: Bacteria can evolve phage resistance. That's interesting

by jobu 10y ago

One of the major critiques of phage therapy is that it will fail the same way antibiotics have failed: Bacteria can evolve phage resistance. That's interesting. Previously I've read that evolution was one of the benefits of phage therapy because phages could evolve alongside the bacteria.

SeanDav 10y ago
Evolution has to work, or else there would be no bacteria left in the world.
kingjacob 10y ago
It is. But technically they are correct. If you just handed out phage freely, as you do abx, bacteria will "eventually" evolve resistance to phage....at a 2-3 orders slower rate, but it will eventually happen. Of course, the solution is easy, you don't develop a phage therapy like you would an antibiotic, but rather like a constantly updating flu vaccine.
- smallnamespace 10y ago
  The 'therapy' might not be handing out pre-grown phages, but literally doing the labwork to isolate and grow phages right in the hospital for each patient. This was how phage therapy was originally developed, and it's still being done that in some surprising places like Georgia [1]. They have phage 'banks' for common bacterial species, and it's not effective, they end up taking bacterial samples from each patient and isolating more phages. [1] https://www.phagetherapycenter.com/pii/PatientServlet?command=static_pttreatinginfections&language=0 https://www.phagetherapycenter.com/pii/PatientServlet?comman...
tgb 10y ago
My impression is that virus evolution is much slower than bacterial evolution. They can't reproduce sexually, so there is no gene recombination to spread beneficial mutations. This difference is partly why vaccines are done for viruses and not so much for bacteria.
- Retric 10y ago
  No, there are plenty of bacterial vaccines. ex: https://en.wikipedia.org/wiki/Typhoid_fever https://en.wikipedia.org/wiki/Typhoid_fever
- maxerickson 10y ago
  The flu vaccine is seasonal because it evolves so quickly. Same with HIV, a high mutation rate complicates making a vaccine. I was really struck by this part of The Great Influenza: https://books.google.com/books?id=BYsW6qTP0pMC&lpg=PP1&pg=PA105#v=onepage&q=mutate&f=false https://books.google.com/books?id=BYsW6qTP0pMC&lpg=PP1&pg=PA... Influenza is an RNA virus. So is HIV and the coronavirus. And of all RNA viruses, influenza and HIV are among those that mutate the fastest. The influenza virus mutates so fast that 99 percent of the 100,000 to 1 million new viruses that burst out of a cell in the reproduction process are too defective to infect another cell and reproduce again. But that still leaves between 1,000 and 10,000 viruses that can infect another cell.
  - tgb 10y ago
    This is very interesting, however, is it answering the right question? HIV and flu vaccine are specifically called out as having unusually high mutation rates. Apparently the difference is between RNA viruses and DNA viruses - the RNA ones have no "double checking" to repair errors, so have much higher mutation rates. The rates quoted here [1] put DNA viruses as similar to humans. I don't know if these phages are RNA or DNA ones (Wikipedia says there are phages of both types and while the T4 virus they have a picture of in the article appears to be DNA-based, they probably just chose it for its striking appearance). More importantly - is mutation rate what we want to consider? Bacteria exchange DNA with each other through horizontal gene transfer and Wikipedia quotes that as the main means of transmitting antibacterial resistance, for example [2], even across species (to the extent that bacterial species are even well-defined). I'm not sure how to make the comparison with that to viral mutation rates. This [3] source gives the following interesting, but imprecise, quote: > This antagonistic coevolution results from the constant emergence of countermeasures by which bacteria resist phages, while phages, mutating at a more rapid rate than their prey, find means to overcome this resistance. The paper it cites [4], definitely shows phage evolution alongside bacteria evolving counter-measures. So I think that's enough to answer the original question posed, though the question of "which is evolving faster" is harder to answer and probably isn't very well-posed. That all said, I know nothing about this field and would be happy for some better insight. [1] http://www.nature.com/nrmicro/journal/v11/n5/box/nrmicro3003_BX1.html http://www.nature.com/nrmicro/journal/v11/n5/box/nrmicro3003... [2] https://en.wikipedia.org/wiki/Horizontal_gene_transfer https://en.wikipedia.org/wiki/Horizontal_gene_transfer [3] http://cid.oxfordjournals.org/content/48/8/1096.full http://cid.oxfordjournals.org/content/48/8/1096.full [4] http://rspb.royalsocietypublishing.org/content/royprsb/269/1494/931.full.pdf http://rspb.royalsocietypublishing.org/content/royprsb/269/1...

by jobu 10y ago

SeanDav 10y ago

Evolution has to work, or else there would be no bacteria left in the world.

kingjacob 10y ago

It is. But technically they are correct. If you just handed out phage freely, as you do abx, bacteria will "eventually" evolve resistance to phage....at a 2-3 orders slower rate, but it will eventually happen. Of course, the solution is easy, you don't develop a phage therapy like you would an antibiotic, but rather like a constantly updating flu vaccine.

smallnamespace 10y ago
The 'therapy' might not be handing out pre-grown phages, but literally doing the labwork to isolate and grow phages right in the hospital for each patient. This was how phage therapy was originally developed, and it's still being done that in some surprising places like Georgia [1]. They have phage 'banks' for common bacterial species, and it's not effective, they end up taking bacterial samples from each patient and isolating more phages. [1] https://www.phagetherapycenter.com/pii/PatientServlet?command=static_pttreatinginfections&language=0 https://www.phagetherapycenter.com/pii/PatientServlet?comman...

tgb 10y ago

My impression is that virus evolution is much slower than bacterial evolution. They can't reproduce sexually, so there is no gene recombination to spread beneficial mutations. This difference is partly why vaccines are done for viruses and not so much for bacteria.

Retric 10y ago
No, there are plenty of bacterial vaccines. ex: https://en.wikipedia.org/wiki/Typhoid_fever https://en.wikipedia.org/wiki/Typhoid_fever
maxerickson 10y ago
The flu vaccine is seasonal because it evolves so quickly. Same with HIV, a high mutation rate complicates making a vaccine. I was really struck by this part of The Great Influenza: https://books.google.com/books?id=BYsW6qTP0pMC&lpg=PP1&pg=PA105#v=onepage&q=mutate&f=false https://books.google.com/books?id=BYsW6qTP0pMC&lpg=PP1&pg=PA... Influenza is an RNA virus. So is HIV and the coronavirus. And of all RNA viruses, influenza and HIV are among those that mutate the fastest. The influenza virus mutates so fast that 99 percent of the 100,000 to 1 million new viruses that burst out of a cell in the reproduction process are too defective to infect another cell and reproduce again. But that still leaves between 1,000 and 10,000 viruses that can infect another cell.
- tgb 10y ago
  This is very interesting, however, is it answering the right question? HIV and flu vaccine are specifically called out as having unusually high mutation rates. Apparently the difference is between RNA viruses and DNA viruses - the RNA ones have no "double checking" to repair errors, so have much higher mutation rates. The rates quoted here [1] put DNA viruses as similar to humans. I don't know if these phages are RNA or DNA ones (Wikipedia says there are phages of both types and while the T4 virus they have a picture of in the article appears to be DNA-based, they probably just chose it for its striking appearance). More importantly - is mutation rate what we want to consider? Bacteria exchange DNA with each other through horizontal gene transfer and Wikipedia quotes that as the main means of transmitting antibacterial resistance, for example [2], even across species (to the extent that bacterial species are even well-defined). I'm not sure how to make the comparison with that to viral mutation rates. This [3] source gives the following interesting, but imprecise, quote: > This antagonistic coevolution results from the constant emergence of countermeasures by which bacteria resist phages, while phages, mutating at a more rapid rate than their prey, find means to overcome this resistance. The paper it cites [4], definitely shows phage evolution alongside bacteria evolving counter-measures. So I think that's enough to answer the original question posed, though the question of "which is evolving faster" is harder to answer and probably isn't very well-posed. That all said, I know nothing about this field and would be happy for some better insight. [1] http://www.nature.com/nrmicro/journal/v11/n5/box/nrmicro3003_BX1.html http://www.nature.com/nrmicro/journal/v11/n5/box/nrmicro3003... [2] https://en.wikipedia.org/wiki/Horizontal_gene_transfer https://en.wikipedia.org/wiki/Horizontal_gene_transfer [3] http://cid.oxfordjournals.org/content/48/8/1096.full http://cid.oxfordjournals.org/content/48/8/1096.full [4] http://rspb.royalsocietypublishing.org/content/royprsb/269/1494/931.full.pdf http://rspb.royalsocietypublishing.org/content/royprsb/269/1...