The self-regulation of the toxin-antitoxin system

May 28th 2019

Researchers at ULB’s Cellular and Molecular Microbiology Laboratory have identified the mechanism that regulates the toxin-antitoxin system of E. coli bacteria.

Toxin-antitoxin (TA) systems are found in the genomes of many bacteria, yet their role is still poorly understood and has been the subject of lively debate in the international microbiology community. As a result, researchers are very interested in these systems.
ULB’s Cellular and Molecular Microbiology Laboratory is collaborating with Estonian and Swedish research teams, among others. Together they have demonstrated that contrary to what the commonly accepted model suggests, E. coli’s 10 classic TA systems are not involved in antibiotic tolerance, nor in stress adaptation processes(1).

A double-edged sword
More recently, researchers at the Laboratory have identified a mechanism that gives new insight into what happens inside the bacteria cell when it produces a TA system.
Professors Abel Garcia-Pino and Laurence Van Melderen head the Cellular and Molecular Microbiology Group, and are especially interested in the pair formed in Escherichia coli by AtaT (toxin) and AtaR (antitoxin). ‘The toxin produced by this TA system is a powerful inhibitor of protein synthesis’, reminds Professor Garcia-Pino. ‘When the AtaT toxin is activated, it inhibits protein synthesis, which eventually results in cell death. This means a very precise regulation mechanism is needed.’

‘Capturing’ a molecule
‘We have found that when the AT pair is produced, the AtaR antitoxin is expressed first’, continues the researcher. ‘When the AtaT toxin is then produced, the antitoxin immediately "catches" and "gags" it.’ This capture is how the antitoxin neutralises the toxin’s activity and prevents it from harming E. coli. But there’s more: ‘The toxin can only activate when the antitoxin is destroyed. So AtaT promotes its own expression as well as that of AtaR.’

Next step: find out the role of TA systems
This discovery was recently published in Nature Chemical Biology(2). ‘Now that we know how E. coli protects itself from its own weapon, the next step is to understand exactly how TA systems work and what role they play inside bacteria.’

(1) These discoveries, as well as the exchanges of views between the various teams involved, were published in journal mBio in 2018.
(2) D. Jurénas et al., ‘Mechanism of regulation and neutralization of the AtaR–AtaT toxin–antitoxin system’, in Nature Chemical Biology, 15, 285–294, 4 February 2019.