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

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--D-glutamic acid (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 DPGA capsular polypeptide. Mice were injected via the intravenous route with various amounts of purified DPGA. Blood, urine, and various organs were harvested at different times after treatment. Sites of DPGA accumulation were determined by immunoassay using monoclonal antibodies specific for DPGA. The results showed that the liver and spleen were the primary sites for the accumulation of 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 DPGA. Unlike capsular polysaccharides, the hepatic sinusoidal endothelial cells were also sites for DPGA accumulation. DPGA was rapidly cleared from serum and was excreted into the urine. DPGA in the urine showed a reduced molecular size relative to native 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 DPGA and capsular polysaccharides include the accumulation of DPGA in hepatic sinusoidal endothelial cells and a DPGA clearance rate that was more rapid than the clearance reported for capsular polysaccharides.

Published ahead of print on 14 January 2008.

Editor: A. Casadevall