📰 Inhibition of the growth of the tuberculosis bacillus by one of its toxins

Some bacteria produce toxins that allow them to control their own growth, thus facilitating rapid adaptation to various stresses or other attacks on the immune system. Scientists have characterized the mechanism of action of one of these toxins present in Mycobacterium tuberculosisthe bacillus of tuberculosis (Tuberculosis is a transmissible, non-immunizing infectious disease, with signs…). The toxin (A toxin is a substance toxic to one or more living organisms. Le Petit Larousse de…) binds to the ribosome and specifically cleaves certain messenger RNAs (mRNAs) during translation. This activity (The term activity can refer to a profession.) is for the first time observed by cryo-electron microscopy. The results are published in the journal NatureCommunications.

Two-component « toxin-antitoxin » (TA) systems include a toxin (the poison) and an antitoxin (the antidote) that neutralizes it. Toxins use very diverse and elegant strategies to slow down or block the bacterial growth (The notion of bacterial growth covers two aspects: the growth of the cell…) mainly targeting essential processes or structures such as the protein synthesis (Protein synthesis is the act by which a cell assembles a chain…)the cell cycle (The cell cycle is the set of phases through which a cell passes between two divisions…) or membranes. Although at this day (The day or the day is the interval which separates the sunrise from the sunset; it is the…) the specific conditions that lead to theenable (Activation may refer to:) of these toxins remain largely unknown, these systems have been implicated in various cellular processes, including the maintenance of genes for virulence (Virulence designates the pathogenic, harmful and violent character of a micro-organism…) and mobile genetic elements, defense against bacteriophages, antibiotic tolerance and virulence. In accordance with these characteristics, the study of the targets and mechanisms of action of these toxins therefore offers new perspectives for the discovery of new antibacterial agents.

The virulence of Mycobacterium tuberculosisthe tuberculosis bacillus, lies mainly in its ability to adapt to the many stresses it encounters during its infectious cycle, in particular its ability to enter a state of persistence ( Persistence (statistics) Persistence (computing) in painting: The…) which allows it to survive in the host without causing sickness (Disease is an alteration of the functions or health of a living organism, animal…) until conditions become more favorable for its spread, as when the immune system (The immune system of an organism is a coordinated set of elements of…) of the host weakens. Remarkably, Mycobacterium tuberculosis has the particularity of having a number (The notion of number in linguistics is treated in the article « Number…) very large number of AT systems (more than 80), which could participate in establishing the phase (The word phase can have several meanings, it is used in several fields and…) of persistence in this bacterium (Bacteria (Bacteria) are prokaryotic unicellular living organisms, characterized…).

Scientists show that once activated, the TAC toxin of Mycobacterium tuberculosis binds to the ribosome and cuts the mRNAs being translated, thus causing a temporary halt in protein synthesis and consequently in the growth of the bacillus. Thanks to cryo-electron microscopy, they were able to observe the toxin for the first time interaction (An interaction is an exchange of information, affects or energy between two agents within…) with the ribosome, a transfer RNA (tRNA) and a native mRNA targeted by this toxin. This structure shows how the toxin enters the ribosome and relies on the tRNA already present to recognize and cleave the mRNA.

This study highlights light (Light is the set of electromagnetic waves visible to the eye…) the mechanism leading to the inhibition of the growth of the tubercle bacillus by a toxin. This very detailed understanding of the mechanism could help to develop potential therapeutic applications, for example in the controlled activation of this toxin in the treatment of tuberculosis.

To know more:
Substrate recognition and cryo-EM 1 structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis
Moise Mansour, Emmanuel Giudice, Xibing Xu, Hatice Akarsu, Patricia Bordes, Valérie Guillet, Donna-Joe Bigot, Nawel Slama, Gaetano D’urso, Sophie Cat (The domestic cat (Felis silvestris catus) is a carnivorous mammal of the family of…)Peter Redder, Laurent Falquet, Lionel Mourey, Reynald Gillet, Pierre Genevaux.
Nature Communications May 12, 2022. https://doi.org/10.1038/s41467-022-30373-w

Laboratories:
Laboratory of Microbiology (Microbiology is a sub-discipline of biology based on the study of…) and of Genetic (Genetics (from the Greek genno γεννώ = to give birth) is…) Molecular, Center for Biology (Biology, commonly called « bio », is the science of life….) Integrative (CBI), (University of Toulouse/CNRS/UPS.
Toulouse, France.
Institute of Genetics and Development of Rennes (IGDR) (University of Rennes/CNRS) – Rennes, France.

contacts:
– Pierre Genevaux – Searcher (A researcher (fem. researcher) refers to a person whose job is to do research…) CNRS (The National Center for Scientific Research, better known by its acronym CNRS, is the largest…) at the Laboratory of Microbiology and Molecular Genetics at the Center for Integrative Biology (CBI) – University (A university is an institution of higher education whose objective is the…) de Toulouse/CNRS/UPS – pierre.genevaux at univ-tlse3.fr
– Reynald Gillet – Lecturer-researcher at theUniversity of Rennes (The University of Rennes, is an old university which finds its origin in…) 1 and to theInstitute (An institute is a permanent organization created for a certain purpose. It is…) Genetics and Development of Rennes (IGDR) – University of Rennes1/CNRS) – reynald.gillet at univ-rennes1.fr