Characterization of a plasmid region involved in Bacillus anthracis toxin production and pathogenesis

The germination of spores within the host is the initial step of anthrax in fection. We have shown, using immunofluorescence staining, confocal scannin g laser microscopy and image cytometry analysis, that the alveolar macropha ge is the primary site of B. anthracis germination in a murine inhalation i nfection model. B. anthracis germinated inside macrophages, in vesicles der ived from the phagosomal compartment. We have demonstrated that the toxin g enes and their trans-activator, AtxA, are expressed within the macrophages after germination. It was also shown that the pXO1 plasmid strongly enhance d capsule formation and that this influence is mediated by AtxA. This indic ates the existence of a regulon where AtxA is the regulatory protein acting on genes located on different plasmids. We identified a tricistronic germi nation operon gerX located between the pag and atxA genes on the 40-kb toxi n-encoding fragment of pXO1. Analysis of a gerX null mutant indicated that gerX-encoded proteins are involved in the virulence of B. anthracis.