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Infection and Immunity, August 2007, p. 3894-3901, Vol. 75, No. 8
0019-9567/07/$08.00+0     doi:10.1128/IAI.00283-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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

John Weaver,1,2,3,{dagger} Tae Jin Kang,4,{dagger} Kimberly W. Raines,1 Guan-Liang Cao,1,2,3 Stephen Hibbs,2 Pei Tsai,1,2,3 Les Baillie,2,5 Gerald M. Rosen,1,2,3 and Alan S. Cross4*

Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201,1 Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201,2 Center for EPR Imaging In Vivo Physiology, University of Maryland School of Pharmacy, Baltimore, Maryland 21201,3 Center for Vaccine Development, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, 21201,4 Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3DF Wales, United Kingdom5

Received 20 February 2007/ Returned for modification 27 February 2007/ Accepted 1 May 2007

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 O2·–, experiments were designed to determine whether NOS 2 formed peroxynitrite (ONOO–) from the reaction of ·NO with O2·– 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.

* Corresponding author. Mailing address: Center for Vaccine Development, Department of Medicine, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF I 480, Baltimore, MD 21201. Phone: (410) 706-5328. Fax: (410) 706-6205. E-mail: across{at}medicine.umaryland.edu

{triangledown} Published ahead of print on 14 May 2007.

Editor: J. B. Bliska

{dagger} J.W. and T.J.K. contributed equally to this study.

Infection and Immunity, August 2007, p. 3894-3901, Vol. 75, No. 8
0019-9567/07/$08.00+0     doi:10.1128/IAI.00283-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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