RASTA-Bacteria

Rapid Automated Scan for Toxins and Antitoxins in Bacteria

Toxins & Antitoxins: Presentation

Toxin/Antitoxin (TA) modules are generally made of two adjacent co-oriented but antagonist genes, where one encodes a stable toxin harmful to an essential cell process, and the second a labile antitoxin, capable of blocking the toxin's aggressive behavior by DNA- or protein-binding. The toxic component can be:

Discovered in 1983 by Ogura and co-workers, they were first called "plasmid addiction systems" as they fulfilled plasmid maintenance. Ten years later, chromosomal homologs were discovered in Escherichia coli (Masuda), renewing interest in them. This lead to the discovery of new systems in various bacteria, and of their implication in programmed cell death (PCD). Aizenman even hypothesized in 1996 that under severe starvation conditions TA-mediated PCD of moribund subpopulations could provide the remaining healthy cells with nutrients, thus benefiting to the specie. In fact, proof was later established that some of them actually provoked a static state in some adverse conditions, with cells being still viable but unable to proliferate, and that this state was fully reversible on cognate antitoxin induction (Pedersen et al. 2002), however possibly within a certain timeframe (Amitai et al. 2004).

Classification

TA systems are presently distributed in 8 families, depending on their structural features or modes of action (Gerdes 2005).

TA Activation

Chromosome-borne TA systems are activated by various extreme conditions, such as:

Indeed, TA modules are believed to fulfill a backup system to the stringent response during stasis. As a reduced translational rate means less translational errors, TA loci most likely function in quality control of gene expression, helping the cells cope with nutritional stress (Gerdes 2005). Therefore, it remains a priority to exhaustively identify TA loci in prokaryotic organisms, in order to improve our comprehension of them and more broadly of the cellular mechanisms behind bacterial adaptation.

Our goal

TA systems, which are widespread among both bacteria and archeae, thus reveal to be of high importance to the prokaryotic world. Their role in programmed cell death moreover constitutes a promising target for the design of a new class of antibiotics. Previous studies have searched for TA in completely sequenced genomes (archaea and eubacteria) based on standard sequence alignment tools (BLASTP and TBLASTN). To overcome the limitation of such methods, and because we are concerned by the lack of annotation of small ORFs, we developed a simple method for identifying all potential TA systems in any given bacterial genome: Rapid Automated Scan for Toxins and Antitoxins in Bacteria (RASTA-Bacteria). Our tool not only relies on the existence of conserved functional domains in toxins and antitoxins, but also takes into account the genomic features of these genes.
We hope our tool's predictions will help scientists increase the knowledge of prokaryotic behaviour.

For further information, please write to Emeric Sevin or Frédérique Hubler.

Disclaimer: as of October 2010, and until at least end of 2011, insufficient credits/mantime have been allocated to RASTA-Bacteria, which is not maintained anymore. If you have any questions, you can try writing to Emeric Sevin but with no guarantee that you'll get an answer soon. We apologize for this situation, and thank you for your understanding.

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Page last modified: November 12, 2014.