Early Bacillus anthracis macrophage interactions: intracellular survival and escape

This study describes early intracellular events occurring during the establ ishment phase of Bacillus anthracis infections. Anthrax infections are init iated by dormant endospores gaining access to the mammalian host and becomi ng engulfed by regional macrophages (M phi). During systemic anthrax, late stage events include vegetative growth in the blood to very high titres and the synthesis of the anthrax exotoxin complex, which causes disease sympto ms and death. Experiments focus on the early events occurring during the fi rst few hours of the B. anthracis infectious cycle, from endospore germinat ion up to and including release of the vegetative cell from phagocytes. We found that newly vegetative bacilli escape from the phagocytic vesicles of cultured M phi and replicate within the cytoplasm of these cells. Release f rom the M phi occurs 4-6 h after endospore phagocytosis, timing that correl ates with anthrax infection of test animals. Genetic analysis from this stu dy indicates that the toxin plasmid pXO1 is required for release from the M phi, whereas the capsule plasmid pXO2 is not. The transactivator atxA, loc ated on pXO1, is also found to be essential for release, but the toxin gene s themselves are not required. This suggests that M phi release of anthrax bacilli is atxA regulated. The putative 'escape' genes may be located on th e chromosome and/or on pXO1.