☠️ When the tuberculosis-causing bacterium makes its own poison

Mycobacterium tuberculosis, the bacterium responsible for tuberculosis, produces pairs of poison-antidote, called "Toxin-Antitoxin" systems, which allow it to control its growth and adapt to stress.

In an article published in Nucleic Acids Research, scientists identified one of these toxins that blocks protein production, thereby causing the death of the bacillus. Stimulating the activity of this toxin could help better fight against some antibiotic-resistant bacterial strains.

Understanding tuberculosis to better fight it

Tuberculosis is the leading cause of death from a single infectious agent: the bacterium Mycobacterium tuberculosis (M. tuberculosis). It primarily affects the lungs and is transmitted from person to person through the air. It can persist for a long time in the body in a dormant, non-replicative, and drug-resistant form: latent tuberculosis.

The emergence of multidrug-resistant and extensively drug-resistant strains has increased the need to identify new targets and innovative treatment strategies to develop new drugs.

M. tuberculosis has a remarkably high number of small two-component genetic modules called Toxin-Antitoxin (TA) systems, nearly 90. These systems consist of a deleterious toxin and an antitoxin that inhibits its activity and acts as an antidote. Under normal conditions, the antitoxin neutralizes the toxin. But under stress, the inhibition by the antitoxin is lifted: the toxins become active and target vital processes such as protein synthesis (translation), replication, metabolism, or cell wall formation, leading to growth inhibition or death of the bacillus.

While some of these systems are involved in the virulence and persistence of the bacillus, their exact role in M. tuberculosis is still poorly understood. Nevertheless, the toxic potency of some of these molecules suggests unprecedented therapeutic potential, either as a new target for drug research or as a direct antimicrobial agent.

New leads thanks to the ReIE toxin

In an article published in the journal Nucleic Acids Research, scientists reveal a remarkable activity within some toxins of the ReIE family. These toxins block the production of proteins, a vital process for bacterial survival. They directly attack the ribosome, the cellular "machine" that assembles proteins from instructions contained in DNA.

Specifically, they cut a small portion of a ribosomal component (ribosomal RNA), which prevents it from correctly binding to messenger RNA molecules, the "blueprints" used to make proteins. Without this step, the bacterium can no longer produce the proteins it needs to grow or reproduce.

This breakthrough opens new therapeutic perspectives: stimulating the activity of the ReIE toxin could help fight the bacterium and counter its increasing resistance to antibiotics.