This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.00283-07v1 75/8/3894    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weaver, J. Articles by Cross, A. S. Search for Related Content PubMed PubMed Citation Articles by Weaver, J. Articles by Cross, A. S.

 Previous Article  |  Next Article 

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

John Weaver,^1,2,3, Tae Jin Kang,^4, 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. Cross^4*

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.

Published ahead of print on 14 May 2007.

Editor: J. B. Bliska

J.W. and T.J.K. contributed equally to this study.

This article has been cited by other articles:

• Stojkovic, B., Torres, E. M., Prouty, A. M., Patel, H. K., Zhuang, L., Koehler, T. M., Ballard, J. D., Blanke, S. R. (2008). High-Throughput, Single-Cell Analysis of Macrophage Interactions with Fluorescently Labeled Bacillus anthracis Spores. Appl. Environ. Microbiol. 74: 5201-5210 [Abstract] [Full Text]  
• Brahmbhatt, T. N., Darnell, S. C., Carvalho, H. M., Sanz, P., Kang, T. J., Bull, R. L., Rasmussen, S. B., Cross, A. S., O'Brien, A. D. (2007). Recombinant Exosporium Protein BclA of Bacillus anthracis Is Effective as a Booster for Mice Primed with Suboptimal Amounts of Protective Antigen. Infect. Immun. 75: 5240-5247 [Abstract] [Full Text]