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How the anthrax bacterium eludes our immune defenses
After having demonstrated the protective role of one of the enzymes of our natural immunity against B. anthracis, the anthrax bacterium, researchers from the Institut Pasteur, Inserm, and the CNRS explain how the bacillus is capable of evading the bactericidal action of this enzyme: this bacterium produces a toxin that inhibits the enzyme synthesis. This research*, published in PloS Pathogens, reveals potential new therapeutic avenues against anthrax.
Paris, december 10, 2007
Bacillus anthracis - en rouge, la capside. en bleu, l'ADN. Anthrax is caused by the bacterium Bacillus anthracis, and affects mammals, including humans. B. anthracis survives in the environment in the form of spores that, once they have entered the organism, can germinate and give rise to bacteria. These bacteria then multiply rapidly, producing toxins. Toxaemia and septicaemia provoked by B. anthracis are fatal in 100% of cases of infection by inhalation, in absence of treatment. This treatment, which consists of antibiotic therapy and intensive care, is not always sufficient to prevent a fatal outcome.
In 2004, researchers from Lhousseine Touqui's group within the Innate Host Defense and Inflammation Unit (Institut Pasteur/INSERM U874), directed by Michel Chignard, as well as Pierre Goossens' team in the Toxins and Bacterial Pathogenesis Unit (Institut Pasteur/CNRS URA2172), directed by Michèle Mock, in collaboration with researchers from the CNRS, demonstrated in vitro and in vivo that the host was naturally equipped to combat the anthrax bacterium. Scientists had, in fact, proven that cells of the immune system, called macrophages, produce an enzyme with bactericidal properties. Within the lungs, this enzyme is produced in sufficient amount to destroy B. anthracis after inhalation. Their experiments have even demonstrated that injecting the enzyme into infected mice made it possible to protect them. However, in spite of the host’s capacity to produce this enzyme, air born infection by B. anthracis remains fatal if not treated. It is thus of a great importance to determine the mechanism(s) by which B. anthracis interfere with the natural host defense.
Researchers discovered that one of the toxins secreted by the bacterium allows it to counter the action of the protective enzyme: this toxin indeed inhibits the synthesis of the enzyme by the lung macrophages, thereby reducing their capacity to kill the bacilli and the germinated spores of B. anthracis. “We were able to determine at the molecular level which mechanisms intervened in inhibiting the synthesis of the enzyme,” explained Touqui and Goossens. “As a result, we hope to be able to identify new therapeutic targets against anthrax. The use of the protective enzyme, which eliminates the bacterium much more rapidly than the antibiotics currently administered, could, for example, represent an interesting strategy.”
* * This research is supported by a grant from the French Foundation for Medical Research (Marianne Josso Prize).
Picture : Bacillus anthracis, causative agent of anthrax. In red, the capside. In bleu, DNA. /// Copyright Institut Pasteur.
Benoît Raymond (1,2), Dominique Leduc (1,2), Lucas Ravaux (3), Ronan Le Goffic (1,2), Thomas Candela (4), Michel Raymondjean (3), Pierre-Louis Goossens (4) and Lhousseine Touqui (1,2).
(1,2) Innate Host Defense and Inflammation Unit, Institut Pasteur/Inserm U874, Paris, France
(3) UMR CNRS 7079 - Physiology and physiopathology, Pierre & Marie Curie University, Paris, France
(4) Toxins and Bacterial Pathogenesis Unit, Institut Pasteur/CNRS, URA-2172, Paris, France.