Talk:CH391L/S12/ToxinAntitoxins

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*'''[[User:Jeffrey E. Barrick|Jeffrey E. Barrick]] 19:01, 26 February 2012 (EST)''':There are many toxin-antitoxin systems in the genomes of pathogens like ''Mycobacterium tuberculosis''. I've heard that they might contribute to the phenomenon of "persistence", but I don't know how the current evidence for this hypothesis weighs versus the evidence that TA modules are selfish elements that are actually slightly deleterious to carry around, but can accumulate in a genome over time during evolution at small population size when selection against slightly deleterious mutations is weak.
*'''[[User:Jeffrey E. Barrick|Jeffrey E. Barrick]] 19:01, 26 February 2012 (EST)''':There are many toxin-antitoxin systems in the genomes of pathogens like ''Mycobacterium tuberculosis''. I've heard that they might contribute to the phenomenon of "persistence", but I don't know how the current evidence for this hypothesis weighs versus the evidence that TA modules are selfish elements that are actually slightly deleterious to carry around, but can accumulate in a genome over time during evolution at small population size when selection against slightly deleterious mutations is weak.
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:*'''[[User:Brian Renda|Brian Renda]] 22:06, 26 February 2012 (EST)''':A somewhat recent publication look at the relationship of persistence and TA loci in ''E. coli'' <cite>Maisonneuve2011</cite>. They found that deleting individual loci had no effect on persistence. However, when they deleted more and more loci, they noticed a correlative drop in persistence. The first significant difference was at about 4-5 loci and at 10 loci deletions, persistence in antibiotics dropped 100-200 fold. They mention in the discussion that this phenomena helps explain the extreme persistence of ''Mycobacterium tuberculosis'', which contains at least 88 TA loci with a heavy preference towards translation inhibitors.  
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:*'''[[User:Brian Renda|Brian Renda]] 22:06, 26 February 2012 (EST)''':A somewhat recent publication look at the relationship of persistence and TA loci in ''E. coli'' <cite>Maisonneuve2011</cite>. They found that deleting individual loci had no effect on persistence. However, when they deleted more and more loci, they noticed a correlative drop in persistence. The first significant difference was at about 4-5 loci and at 10 loci deletions, persistence in antibiotics dropped 100-200 fold. They mention in the discussion that this phenomena helps explain the extreme persistence of ''Mycobacterium tuberculosis'', which contains at least 88 TA loci with a heavy preference towards translation inhibitors. When you combine this with the discovery that MazF expression leads to selective expression of a few stress and cell death proteins through a pretty cool lmRNA-modified ribosome mechanism <cite>Vesper2011</cite> suggests that at least some TA loci are beneficial for the cell. It is interesting to consider if the loss of these TA loci would be favored without exposure to stressful environments (perhaps one could look for variation in the long term lines?) A mechanism to maintain them could be their regulation: many loci are regulated by their antitoxin or antitoxin-toxin complex. Perhaps mutations that cause diminished function in the toxins also effect antitoxin binding, resulting in runaway expression of the slightly-diminished but still somewhat functional toxin.  
*'''[[User:Adam Meyer|Adam Meyer]] 21:55, 26 February 2012 (EST)''':Are there any instances of labs/companies using a TA system (A) in the place of antibiotics or (B) as a failsafe or intellectual property protection method?
*'''[[User:Adam Meyer|Adam Meyer]] 21:55, 26 February 2012 (EST)''':Are there any instances of labs/companies using a TA system (A) in the place of antibiotics or (B) as a failsafe or intellectual property protection method?

Revision as of 22:12, 26 February 2012


  • Jeffrey E. Barrick 00:14, 25 February 2012 (EST):Please, italicize species names like E. coli.
  • Jeffrey E. Barrick 19:01, 26 February 2012 (EST):There are many toxin-antitoxin systems in the genomes of pathogens like Mycobacterium tuberculosis. I've heard that they might contribute to the phenomenon of "persistence", but I don't know how the current evidence for this hypothesis weighs versus the evidence that TA modules are selfish elements that are actually slightly deleterious to carry around, but can accumulate in a genome over time during evolution at small population size when selection against slightly deleterious mutations is weak.
  • Brian Renda 22:06, 26 February 2012 (EST):A somewhat recent publication look at the relationship of persistence and TA loci in E. coli [1]. They found that deleting individual loci had no effect on persistence. However, when they deleted more and more loci, they noticed a correlative drop in persistence. The first significant difference was at about 4-5 loci and at 10 loci deletions, persistence in antibiotics dropped 100-200 fold. They mention in the discussion that this phenomena helps explain the extreme persistence of Mycobacterium tuberculosis, which contains at least 88 TA loci with a heavy preference towards translation inhibitors. When you combine this with the discovery that MazF expression leads to selective expression of a few stress and cell death proteins through a pretty cool lmRNA-modified ribosome mechanism [2] suggests that at least some TA loci are beneficial for the cell. It is interesting to consider if the loss of these TA loci would be favored without exposure to stressful environments (perhaps one could look for variation in the long term lines?) A mechanism to maintain them could be their regulation: many loci are regulated by their antitoxin or antitoxin-toxin complex. Perhaps mutations that cause diminished function in the toxins also effect antitoxin binding, resulting in runaway expression of the slightly-diminished but still somewhat functional toxin.
  • Adam Meyer 21:55, 26 February 2012 (EST):Are there any instances of labs/companies using a TA system (A) in the place of antibiotics or (B) as a failsafe or intellectual property protection method?


  1. pmid= 21788497 [Maisonneuve2011]
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