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-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.
Weaver
John
J
Center for Vaccine Development, Department of Medicine, University of Maryland School of Medicine, 685 W. Baltimore Street, Baltimore, MD 21201, USA.
Kang
Tae Jin
TJ
Raines
Kimberly W
KW
Cao
Guan-Liang
GL
Hibbs
Stephen
S
Tsai
Pei
P
Baillie
Les
L
Rosen
Gerald M
GM
Cross
Alan S
AS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D001408:Bacillus anthracis / Q000276:immunology*; D002478:Cells, Cultured; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D050296:Microbial Viability; D009569:Nitric Oxide / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013171:Spores, Bacterial / Q000201:enzymology / Q000502:physiology
D000900:Anti-Bacterial Agents; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide