Order from disorder: a bacterial transcription regulation story
14/02/2019
In a study published in Nature Chemical Biology Abel Garcia-Pino WELBIO investigator at the Université libre de Bruxelles and colleagues from the Cellular and Molecular Microbiology team from the ULB provided for the first time experimental evidence to a long held hypothesis on small bacterial operons encoding a toxin and a corresponding neutralizing antitoxin, so-called toxin-antitoxins (TA) modules: antitoxins act as chaperones that can trap toxins while they are produced by the ribosome.
 
Toxin-antitoxin (TA) modules (TA) are widespread in bacterial genomes. They are in particular involved in bacterial « persistence », a phenomenon which allows bacteria to survive antibiotics by slowing down their growth.

In a study published in Nature Chemical Biology Abel Garcia-Pino WELBIO investigator at the Université libre de Bruxelles and colleagues from the Cellular and Molecular Microbiology team from the ULB provided for the first time experimental evidence to a long held hypothesis on toxin-antitoxins (TA) modules, small bacterial operons encoding a toxin and a corresponding neutralizing antitoxin : antitoxins act as chaperones that can trap toxins while they are produced by the ribosome. The antitoxin binds and neutralizes the toxin via its intrinsically disordered C-terminal region (IDR).

This regulatory process is very nuanced. The chaperone action of antitoxins is intricately linked with the regulation of transcription of the TA operon. When the antitoxin traps the monomeric toxin right after its has been translated, the complex inhibits the transcription of the operon. When the antitoxin level decreases, active toxin dimers are formed, the ratio between the toxin and the antitoxin changes and transcription is de-repressed. The antitoxin level can rise again. This strategy has been independently selected several times during bacterial evolution, and different versions have been described for other unrelated TA modules with the presence of an intrinsically disordered region (IDR) as the common factor. These features suggest that these stoichiometric interplays in the antitoxin-toxin ratio are a form of epigenetics that may condition the phenotype of the bacterial offspring in a form of “chemical memory”.
The novel concepts described in this work for the regulation of TA modules are thus of general interest and may be applicable for the regulation of other biological systems.

Article references : Abel Garcia-Pino et al. (2019) Mechanism of regulation and neutralization of the AtaR–AtaT toxin–antitoxin system https://doi.org/10.1038/s41589-018-0216-z


Last update : 14/2/2019 - Vie privée - Printable version -  © 2019 WELBIO

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