Addiction module

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.

The antitoxin is generally less stable than the toxin due to its degradation by proteases already present in the cell. For example, in the ccdAB proteic addiction module, the Lon protease degrades the antitoxin, but also serves many unrelated proteolytic roles, such as degrading oxidated mitochondrial products. This may indicate that the development of these addiction molecules "co-opted" existing cell utilities. The antitoxin in proteic addiction modules functions by binding directly to the toxin and preventing its mode of action. Once the antitoxin has bound to the toxin, the toxin prevents the proteases normally responsible for degrading antitoxin to do so, maintaining the neutralization of that individual toxin molecule.

• 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.
• Par stability determinant: Two small RNAs are transcribed simultaneously from opposite ends of a gene towards a bi-directional terminator. The two products, RNA I (toxin) and RNA II (antitoxin) immediately form a stable complex where RNA II binds (and occludes) the ribosome binding site of RNA I, preventing translation of RNA I and thus production of toxin.