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Germination of Bacillus anthracis spores within alveolar macrophages
C Guidi-Rontani1, M Weber-Levy, E Labruyère
1Unité Toxines et Pathogénie Bactériennes, CNRS URA1858, Institut Pasteur, Paris, France. rontani@pasteur.fr
Abstract:
The fatal character of the infection caused by inhalation of Bacillus anthracis spores results from a complex pathogenic cycle involving the synthesis of toxins by the bacterium. We have shown using immunofluorescent staining, confocal scanning laser microscopy and image cytometry analysis that the alveolar macrophage was the primary site of B. anthracis germination in a murine inhalation infection model. Bacillus anthracis germinated inside murine macrophage-like RAW264.7 cells and murine alveolar macrophages. Germination occurred in vesicles derived from the phagosomal compartment. We have also demonstrated that the toxin genes and their trans-activator, AtxA, were expressed within the macrophages after germination.
Insights
Bacillus anthracis spores germinate within alveolar macrophages, initiating infection. Toxin gene expression occurs inside these cells after germination, contributing to the fatal nature of anthrax.
Area of Science:
- Immunology
- Microbiology
- Pathogenesis
Background:
- Inhalational anthrax is a severe infection caused by Bacillus anthracis spores.
- The bacterium's pathogenic cycle involves toxin synthesis, leading to fatal outcomes.
- Understanding the initial site of germination is crucial for developing countermeasures.
Purpose of the Study:
- To identify the primary site of Bacillus anthracis germination in a murine inhalation model.
- To investigate the intracellular location of germination and subsequent toxin gene expression.
Main Methods:
- Immunofluorescent staining
- Confocal scanning laser microscopy
- Image cytometry analysis
- Murine inhalation infection model using RAW264.7 cells and alveolar macrophages
Main Results:
- Alveolar macrophages and RAW264.7 cells were identified as the primary sites for B. anthracis germination.
- Germination was observed within vesicles derived from the phagosomal compartment.
- Expression of B. anthracis toxin genes and the AtxA trans-activator was detected within macrophages post-germination.
Conclusions:
- Alveolar macrophages are a critical early host cell in B. anthracis inhalation infections.
- Intracellular germination and subsequent toxin gene expression within macrophages contribute to anthrax pathogenesis.
- Targeting intracellular events in macrophages may offer therapeutic strategies against anthrax.