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Infection and Immunity, March 2008, p. 899-906, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01176-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

In Vivo Fate and Distribution of Poly-{gamma}-D-Glutamic Acid, the Capsular Antigen from Bacillus anthracis{triangledown}

Marjorie D. Sutherland,1,2 Peter Thorkildson,1 Samuel D. Parks,3 and Thomas R. Kozel1,2*

Department of Microbiology and Immunology,1 Cell and Molecular Biology Program,2 Department of Pathology, University of Nevada School of Medicine, Reno, Nevada 895573

Received 24 August 2007/ Returned for modification 1 October 2007/ Accepted 27 December 2007

Bacillus anthracis is surrounded by an antiphagocytic capsule composed of poly-{gamma}-D-glutamic acid ({gamma}DPGA). Bacterial and fungal capsular polysaccharides are shed into body fluids in large amounts during infection. The goal of our study was to examine the in vivo fate and distribution of the {gamma}DPGA capsular polypeptide. Mice were injected via the intravenous route with various amounts of purified {gamma}DPGA. Blood, urine, and various organs were harvested at different times after treatment. Sites of {gamma}DPGA accumulation were determined by immunoassay using monoclonal antibodies specific for {gamma}DPGA. The results showed that the liver and spleen were the primary sites for the accumulation of {gamma}DPGA. As found in previous studies of capsular polysaccharides, the Kupffer cells of the liver and splenic macrophages were sites for the cellular accumulation of {gamma}DPGA. Unlike capsular polysaccharides, the hepatic sinusoidal endothelial cells were also sites for {gamma}DPGA accumulation. {gamma}DPGA was rapidly cleared from serum and was excreted into the urine. {gamma}DPGA in the urine showed a reduced molecular size relative to native {gamma}DPGA. The results indicate that in vivo clearance of the polypeptide capsular antigen of B. anthracis shares several features with the clearance of capsular polysaccharides. Key differences between the in vivo behaviors of {gamma}DPGA and capsular polysaccharides include the accumulation of {gamma}DPGA in hepatic sinusoidal endothelial cells and a {gamma}DPGA clearance rate that was more rapid than the clearance reported for capsular polysaccharides.


* Corresponding author. Mailing address: Department of Microbiology and Immunology/320, University of Nevada School of Medicine, Reno, NV 89557. Phone: (775) 784-4124. Fax: (775) 327-2332. E-mail: tkozel{at}medicine.nevada.edu

{triangledown} Published ahead of print on 14 January 2008.

Editor: A. Casadevall


Infection and Immunity, March 2008, p. 899-906, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01176-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Sutherland, M. D., Kozel, T. R. (2009). Macrophage Uptake, Intracellular Localization, and Degradation of Poly-{gamma}-D-Glutamic Acid, the Capsular Antigen of Bacillus anthracis. Infect. Immun. 77: 532-538 [Abstract] [Full Text]