Talk:CH391L/S12/ToxinAntitoxins

• 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.

• Brian Renda 14:47, 5 March 2012 (EST):Relevant literature discussing the theories around TA functioning as selfish DNA elements - mostly in support that they do [3].

• Brian Renda 22:41, 26 February 2012 (EST):Also I should mention that in the persistence paper, over expression of the toxins resulted in increased persistence.

• 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?

• Brian Renda 14:32, 5 March 2012 (EST): A) Yes, see citation [4]. They use a plasmid located ccd antitoxin to repress the transcription of a chromosomally located ccd toxin, eliminating the majority of the metabolic costs of the system. B) Check out the discussion on the Kroll 2010 minireview posted in the main section. Basically, most of the focus has been on failsafes for bioremediation applications but there has not been functionally applied to IP as far as I can tell.

1. Maisonneuve E, Shakespeare LJ, Jørgensen MG, and Gerdes K. Bacterial persistence by RNA endonucleases. Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13206-11. DOI:10.1073/pnas.1100186108 |

   Bacterial persistence by RNA endonucleases

2. Vesper O, Amitai S, Belitsky M, Byrgazov K, Kaberdina AC, Engelberg-Kulka H, and Moll I. Selective translation of leaderless mRNAs by specialized ribosomes generated by MazF in Escherichia coli. Cell. 2011 Sep 30;147(1):147-57. DOI:10.1016/j.cell.2011.07.047 |

   Selective translation of leaderless mRNAs by specialized ribosomes generated by MazF in Escherichia coli.

4. Stieber D, Gabant P, and Szpirer C. The art of selective killing: plasmid toxin/antitoxin systems and their technological applications. Biotechniques. 2008 Sep;45(3):344-6. DOI:10.2144/000112955 |

   The art of selective killing: plasmid toxin/antitoxin systems and their technological applications

5. Van Melderen L and Saavedra De Bast M. Bacterial toxin-antitoxin systems: more than selfish entities?. PLoS Genet. 2009 Mar;5(3):e1000437. DOI:10.1371/journal.pgen.1000437 |

   Bacterial toxin-antitoxin systems: more than selfish entities?