Protective Role of Bacillus anthracis Exosporium in Macrophage-Mediated Killing by Nitric Oxide

Abstract

ABSTRACT 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-dependent bactericidal response. Since NOS 2 also generates O 2 · − , experiments were designed to determine whether NOS 2 formed peroxynitrite (ONOO − ) from the reaction of ·NO with O 2 · − 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 levels in the macrophage. Thus, the ability of B. anthracis to subvert ·NO production has important implications in the control of B. anthracis -induced infection.