Talk:CH391L/S13/Phage Therapy

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*'''[[User:Catherine I. Mortensen|Catherine I. Mortensen]] 14:43, 26 March 2013 (EDT)''':There's always a chance that bacteria can mutate and become resistant to antibiotics such as amoxicillin. What if viruses were used to reverse bacterial resistance to certain antibiotics in combination with antibiotics... so phage therapy and antibiotics used together. This would really kill a disease. Here's an article about reversing bacterial resistance to antibiotics [http://aem.asm.org/content/78/3/744.full]
*'''[[User:Catherine I. Mortensen|Catherine I. Mortensen]] 14:43, 26 March 2013 (EDT)''':There's always a chance that bacteria can mutate and become resistant to antibiotics such as amoxicillin. What if viruses were used to reverse bacterial resistance to certain antibiotics in combination with antibiotics... so phage therapy and antibiotics used together. This would really kill a disease. Here's an article about reversing bacterial resistance to antibiotics [http://aem.asm.org/content/78/3/744.full]
**'''[[User:Kevin Baldridge|Kevin Baldridge]] 11:25, 28 March 2013 (EDT)''':Cool idea, I like their application idea for using it as a surface disinfectant in high-risk areas for antibiotic resistance, i.e. hospitals. However, I wonder how long it will be effective before bacteria adapt a response to the phage? They adapted to antibiotics, and we know they have an innate "immune system" [http://www.sciencemag.org.ezproxy.lib.utexas.edu/content/315/5819/1709.short CRISPR paper in Science 2007] which helps them adapt to viral assault.
**'''[[User:Kevin Baldridge|Kevin Baldridge]] 11:25, 28 March 2013 (EDT)''':Cool idea, I like their application idea for using it as a surface disinfectant in high-risk areas for antibiotic resistance, i.e. hospitals. However, I wonder how long it will be effective before bacteria adapt a response to the phage? They adapted to antibiotics, and we know they have an innate "immune system" [http://www.sciencemag.org.ezproxy.lib.utexas.edu/content/315/5819/1709.short CRISPR paper in Science 2007] which helps them adapt to viral assault.
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**'''[[User:Jeffrey E. Barrick|Jeffrey E. Barrick]] 23:21, 28 March 2013 (EDT)''':Like the paper. It seems like it would be hard to get any system for adding a gene to existing organisms so effective that it would make 100% of them susceptible to an antibiotic.  
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**'''[[User:Jeffrey E. Barrick|Jeffrey E. Barrick]] 23:21, 28 March 2013 (EDT)''':Like the paper. It seems like it would be hard to get any system for adding a gene to existing organisms so effective that it would make 100% of them susceptible to an antibiotic.
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***'''[[User:Neil R Gottel|Neil R Gottel]] 15:39, 31 March 2013 (EDT)''':Agreed. The use of phage therapy would be to increase the number of research avenues to pursue when guarding against bacterial infection. The real silver bullet would be hospitals that entirely closed systems. Or nanites.
*'''[[User:Jeffrey E. Barrick|Jeffrey E. Barrick]] 23:21, 28 March 2013 (EDT)''':Neil, you make it sound like it's easy to find or create a phage capable of killing any bacterium. Where do I find the phage that I use to tailor my microbiota? Are there any groups of bacteria that just don't get infected by phage?
*'''[[User:Jeffrey E. Barrick|Jeffrey E. Barrick]] 23:21, 28 March 2013 (EDT)''':Neil, you make it sound like it's easy to find or create a phage capable of killing any bacterium. Where do I find the phage that I use to tailor my microbiota? Are there any groups of bacteria that just don't get infected by phage?
**'''[[User:Neil R Gottel|Neil R Gottel]] 15:35, 31 March 2013 (EDT)''':Joke answer: contact [http://phagesdb.org/phagehunters/ The Phage Hunters!] A more serious approach would be to first determine what your microbiota looks like using 16S rRNA next-gen sequencing, followed by isolation and screening of individual strains. Once you've found some strains you want to target (maybe you've got some species that has been associated with a higher risk of colon cancer), then we'd start screening lawns of those targeted bacteria against an array of 1 μm filtered environmental samples. I'd start by using filtrates from soil and sewage treatment plants. Maybe even other people! Once we start seeing plaque formation, the phage can be isolated for further study. Ideally we'd have several related strains of phage, which we could gene shuffle, mutate, or rationally design, in order to prepare a phage cocktail with a variety of slightly dissimilar phage (the goal of using a variety of slightly different phage is to take out different variants of the targeted bacterial strain, and reduce the risk of survivors remaining). The phage cocktail is administered, and your microbial community is monitored for any changes.
**'''[[User:Neil R Gottel|Neil R Gottel]] 15:35, 31 March 2013 (EDT)''':Joke answer: contact [http://phagesdb.org/phagehunters/ The Phage Hunters!] A more serious approach would be to first determine what your microbiota looks like using 16S rRNA next-gen sequencing, followed by isolation and screening of individual strains. Once you've found some strains you want to target (maybe you've got some species that has been associated with a higher risk of colon cancer), then we'd start screening lawns of those targeted bacteria against an array of 1 μm filtered environmental samples. I'd start by using filtrates from soil and sewage treatment plants. Maybe even other people! Once we start seeing plaque formation, the phage can be isolated for further study. Ideally we'd have several related strains of phage, which we could gene shuffle, mutate, or rationally design, in order to prepare a phage cocktail with a variety of slightly dissimilar phage (the goal of using a variety of slightly different phage is to take out different variants of the targeted bacterial strain, and reduce the risk of survivors remaining). The phage cocktail is administered, and your microbial community is monitored for any changes.

Revision as of 14:39, 31 March 2013

  • Gabriel Wu 17:23, 25 March 2013 (EDT): Is there a review (in English) of all these Russian studies?
    • Neil R Gottel 13:48, 26 March 2013 (EDT):Yep! Its my first reference. I'll make a note in the article about that.
  • Jeffrey E. Barrick 21:34, 25 March 2013 (EDT):Phage therapy turns up in early 20th century novel about science by Sinclair Lewis: Arrowsmith (not to be confused with Upton Sinclair of The Jungle).
    • Neil R Gottel 13:48, 26 March 2013 (EDT):Cool! Wikipedia says its the earliest novel to focus on scientific culture. We should discuss it at the inaugural meeting of the Barrick Lab Book Club.
      • Jeffrey E. Barrick 23:21, 28 March 2013 (EDT):The inaugural slot is already reserved for Moby Dick.
  • Catherine I. Mortensen 14:43, 26 March 2013 (EDT):There's always a chance that bacteria can mutate and become resistant to antibiotics such as amoxicillin. What if viruses were used to reverse bacterial resistance to certain antibiotics in combination with antibiotics... so phage therapy and antibiotics used together. This would really kill a disease. Here's an article about reversing bacterial resistance to antibiotics [1]
    • Kevin Baldridge 11:25, 28 March 2013 (EDT):Cool idea, I like their application idea for using it as a surface disinfectant in high-risk areas for antibiotic resistance, i.e. hospitals. However, I wonder how long it will be effective before bacteria adapt a response to the phage? They adapted to antibiotics, and we know they have an innate "immune system" CRISPR paper in Science 2007 which helps them adapt to viral assault.
    • Jeffrey E. Barrick 23:21, 28 March 2013 (EDT):Like the paper. It seems like it would be hard to get any system for adding a gene to existing organisms so effective that it would make 100% of them susceptible to an antibiotic.
      • Neil R Gottel 15:39, 31 March 2013 (EDT):Agreed. The use of phage therapy would be to increase the number of research avenues to pursue when guarding against bacterial infection. The real silver bullet would be hospitals that entirely closed systems. Or nanites.
  • Jeffrey E. Barrick 23:21, 28 March 2013 (EDT):Neil, you make it sound like it's easy to find or create a phage capable of killing any bacterium. Where do I find the phage that I use to tailor my microbiota? Are there any groups of bacteria that just don't get infected by phage?
    • Neil R Gottel 15:35, 31 March 2013 (EDT):Joke answer: contact The Phage Hunters! A more serious approach would be to first determine what your microbiota looks like using 16S rRNA next-gen sequencing, followed by isolation and screening of individual strains. Once you've found some strains you want to target (maybe you've got some species that has been associated with a higher risk of colon cancer), then we'd start screening lawns of those targeted bacteria against an array of 1 μm filtered environmental samples. I'd start by using filtrates from soil and sewage treatment plants. Maybe even other people! Once we start seeing plaque formation, the phage can be isolated for further study. Ideally we'd have several related strains of phage, which we could gene shuffle, mutate, or rationally design, in order to prepare a phage cocktail with a variety of slightly dissimilar phage (the goal of using a variety of slightly different phage is to take out different variants of the targeted bacterial strain, and reduce the risk of survivors remaining). The phage cocktail is administered, and your microbial community is monitored for any changes.
    • Neil R Gottel 15:35, 31 March 2013 (EDT):For your second question: a brief search fails to turn up anything. However, I suspect certain environments would make it impossible for phage to survive for long periods of time outside a host, such as radioactive environments. Since phage can't repair their genomes as they're floating around looking for a host, we can imagine a combination of high radiation and low bacterial density that makes it impossible for an infection to propagate. Therefore, we should take a field trip to Chernobyl and do some metagenomic sampling.
  • Thomas Wall 23:46, 28 March 2013 (EDT): So this wasn't the article I was looking for, I remember reading one on clostridium difficile (http://www.pnas.org/content/early/2012/10/04/1206136109). But, this sort of thing led me to wondering if we could engineer probiotic mixtures to make phage against all kinds of things we don't want in our guts.
  • Neil R Gottel 15:35, 31 March 2013 (EDT):Found a 2012 paper that describes a naturally occurring example of the "Ecolicence to Kill" iGEM project (without the weird conjugation part of it). It's a gut bacterium that uses prophage to kill other competing strains.
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