Protective role of Bacillus anthracis exosporium in macrophage-mediated killing by nitric oxide

`The ability of the endospore-forming, gram-positive bacterium Bacillus anthracis to survive in activated macrophages is key to its germination and survival. In a previous publication, we discovered that exposure of primary murine macrophages to B. anthracis endospores upregulated NOS 2 concomitant with an (NO)-N-center dot-dependent bactericidal response. Since NOS 2 also generates O-2(center dot-), experiments were designed to determine whether NOS 2 formed peroxynitrite (ONOO-) from the reaction of (NO)-N-center dot with O-2(center dot-) and if so, was ONOO- microbicidal toward B. anthracis. Our findings suggest that ONOO- was formed upon macrophage infection by B. anthracis endospores; however, ONOO- does not appear to exhibit microbicidal activity toward this bacterium. In contrast, the exosporium of B. anthracis, which exhibits arginase activity, protected B. anthracis from macrophage- mediated killing by decreasing (NO)-N-center dot levels in the macrophage. Thus, the ability of B. anthracis to subvert (NO)-N-center dot production has important implications in the control of B. anthracis- induced infection.