In the framework of a successful Sinergia collaboration funded by the SNSF on studying toxins and antitoxins in bacteria, the group of Dr Laurent Falquet recently published an important article describing TASmania, a new database. Their results validated six out of eleven studied putative new TAs (Toxin-Antitoxin Systems) of Mycobacterium tuberculosis tested in vivo at Prof. Genevaux lab in Toulouse. Mycobacterium tuberculosis is the causative agent of tuberculosis.
Having a Toxin-Antitoxin Systems (TAS) in a bacterium is like having the poison and its antidote at the same place. The antitoxin will prevent the cell death. The TAS are involved in several key biological functions in bacteria (e.g., persistence, plasmid maintenance, phage defense). They have been described in nearly all phyla (rank of classification) and have been classified in six different types based on the activity and molecular type (non-coding RNA or protein) of their components. "The discovery of new TAs in this pathogenic bacterium is really surprising because it was really unlikely to make discoveries on a so well studied organism. It opens the door to other promising findings on less usual organisms.", says Dr Falquet.
A unique discovery mode
Dr. Hatice Akarsu-Egger developed a method to extract potential new Toxin-Antitoxin pairs from ENSEMBL Bacteria, which is a reference bacterial genome database, and organized the candidate genes in a database called TASmania. TASmania offers an extensive annotation of TA loci in a very large database of bacterial genomes, which represents a resource of crucial importance for the world microbiology community. Indeed TASmania supports:
- the discovery of new TA families, contrary to the Chinese database TADB2 that only collects known and validated TAS
- the design of a robust experimental strategy by taking into account potential interferences in trans, that means by making the potential mistakes visible;
- the comparative analysis between TA loci content, phylogeny and/or phenotypes (pathogenicity, persistence, stress resistance, associated host types) in a really quick way by providing a vast repertoire of annotated assemblies. (>41'000)
This database contains TA annotations of a given strain not only mapped to its core genome but also to its plasmids, whenever applicable.
Why is it important?
TAS not only have the potential to kill bacteria, but could also be responsible for the stabilization of resistance. Indeed, the TAS can induce an antibiotic resistance by putting the bacteria in dormancy. From that point of view, it is different from the classical antibiotic resistance. When a cell is in dormancy, it does not divide anymore. Antibiotics mainly target the cells that are dividing. So understanding TAS is a crucial issue in the fight against antibiotic resistance.
What is the next step?
The research began 3 years ago with baseline data. Since then other data have been published. The next task of Prof. Falquet’s lab is to take into account these new data in order to have this tool continually updated.
- TASmania is available for free here
- Related article: “TASmania: A bacterial Toxin-Antitoxin Systems database”
- Falquet group web page.