Great work! Why exactly would you want to mimic the pH of stomach acid in testing the phage? Would it also need to be tested at pH’s found in the blood/rest of the body?
Thank you so much for your question. I could have better explained, but it would be important to test phage stability in low pH levels akin to stomach acid in oral delivery methods in order to ensure the phage could survive in such harsh conditions. Phage therapy can be administered subcutaneously, via surgical drain, or by mouth. This just touched upon that last bit. As far as pH levels found in other parts of the body are concerned, I do believe that testing those would also be important, however, in one case study I read, phages were tested at both high and low pH levels and at various temperatures, but the two variables were never tested together, which I think would be crucial to understanding phage viability in the human body.
Couldn’t comment on P18-Jarnagin, so I’m commenting here. Higher temperatures are often tested to evaluate their effect on phages thermal-stability. Do you expect there to be evidence of reconstitution during cooling phase after exposure to high temperatures?
Hi Alyssa, sorry for the late response, there were a lot of technical difficulties! I understand what you’re getting at, but if we were testing conditions similar to the human body, there wouldn’t be a cooling phase except in the case of a fever reducing. I’m not completely confident in this area of research, but my guess would be that the goal is generation of phages would be the goal in higher temperatures, therefore recombination would not be the result of cooling temperatures.
Thanks for your question. SteveFJ could be modified by deactivating its repressor protein. The repressor protein is what prevents a temperate phage from expressing genes and entering a lytic cycle and thus reproducing and lysing the host bacterial cell. The repressor can be deactivated with the help of environmental stressors such as pH level. SteveFJ isn’t ideal as is, but clearly this phage might not entirely be a lost cause!
Great work! Why exactly would you want to mimic the pH of stomach acid in testing the phage? Would it also need to be tested at pH’s found in the blood/rest of the body?
Hi Tyler,
Thank you so much for your question. I could have better explained, but it would be important to test phage stability in low pH levels akin to stomach acid in oral delivery methods in order to ensure the phage could survive in such harsh conditions. Phage therapy can be administered subcutaneously, via surgical drain, or by mouth. This just touched upon that last bit. As far as pH levels found in other parts of the body are concerned, I do believe that testing those would also be important, however, in one case study I read, phages were tested at both high and low pH levels and at various temperatures, but the two variables were never tested together, which I think would be crucial to understanding phage viability in the human body.
I hope that helps!
Cheers,
Avalon
Couldn’t comment on P18-Jarnagin, so I’m commenting here. Higher temperatures are often tested to evaluate their effect on phages thermal-stability. Do you expect there to be evidence of reconstitution during cooling phase after exposure to high temperatures?
Hi Alyssa,
I have passed this comment along to Jay. I hope she responds.
Cheers,
Avalon
Hi Alyssa, sorry for the late response, there were a lot of technical difficulties! I understand what you’re getting at, but if we were testing conditions similar to the human body, there wouldn’t be a cooling phase except in the case of a fever reducing. I’m not completely confident in this area of research, but my guess would be that the goal is generation of phages would be the goal in higher temperatures, therefore recombination would not be the result of cooling temperatures.
You mention that lytic phages are preferred for phage therapy – how might a temperate phage like SteveFJ be modified for potential therapeutic use?
Hi Alex,
Thanks for your question. SteveFJ could be modified by deactivating its repressor protein. The repressor protein is what prevents a temperate phage from expressing genes and entering a lytic cycle and thus reproducing and lysing the host bacterial cell. The repressor can be deactivated with the help of environmental stressors such as pH level. SteveFJ isn’t ideal as is, but clearly this phage might not entirely be a lost cause!
Cheers,
Avalon