Addiction module
Addiction modules are
Proteic addiction modules
Proteic addiction modules use proteins as toxins and antitoxins, as opposed to RNA or other methods. The known proteic addiction modules all have similar shared characteristics, including placement of the antitoxin gene relative to the toxin gene, method of toxin neutralization by the antitoxin, and autoregulation of the addiction module by the antitoxin or toxin:antitoxin complex.
Transcriptional control of antitoxin:toxin ratios
In protein-based addiction modules, the genes encoding the toxin and antitoxin lie adjacent to each other and are continuously expressed under one operon. To ensure survival of the host when the addiction module is present, more antitoxin must be produced than toxin (to counter the shorter lifespan of the antitoxin molecules). Safe ratios of the toxin and antitoxin are maintained at least in part by both this overexpression and by having the antitoxin-encoding gene encoded upstream from the toxin gene, so that the antitoxin is available to immediately neutralize the toxin. This upstream placement of the antitoxin gene is found in all proteic addiction modules. In addition, the transcription of the whole addiction module is often negatively autoregulated (i.e. the presence of its products decreases its transcriptional rate) by the formation of toxin:antitoxin complexes.
Characteristics of antitoxin molecules
The antitoxin is generally less stable than the toxin due to its degradation by
Antisense RNA addiction modules
Antisense RNA-type addiction modules use a regulatory strand of RNA which is at least partially "antisense" (having complementary base pair encoding) to bind to toxin RNA, and thus prevent toxin translation. This antisense RNA molecule plays the role of antitoxin, similar to the proteic equivalent described above, and is similarly degraded at a faster rate than the toxin mRNA it inhibits. In addition, the transcription of the antitoxin RNA is heavily upregulated by a strong
Examples
- Hok/sok system: The transcription of sok (suppression of killing) RNA allows it to bind to a region that overlaps the open reading frame of the hok (host killing) toxin RNA.
- ribosome binding siteof RNA I, preventing translation of RNA I and thus production of toxin.
See also
- hok/sok system, an example of addiction module
- Plasmid mediated resistance
References
Engelberg-Kulka, Hanna; Gad Glaser (October 1999). "Addiction modules and programmed cell death and antideath in bacterial cultures". Annual Review of Microbiology. 53. Annual Reviews: 43–70.
Shokeen, Sonia; Greenfield, Tony J; Ehli, Erik A; Rasmussen, Jessica; Perrault, Brian E; Weaver, Keith E. (March 2009). "An Intramolecular Upstream Helix Ensures the Stability of a Toxin-Encoding RNA in Enterococcus faecalis". Journal of Bacteriology. 191 (5). American Society for Microbiology: 1528–1536.