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Antimicrobial Agents and Chemotherapy, March 2008, p. 1014-1020, Vol. 52, No. 3
0066-4804/08/$08.00+0     doi:10.1128/AAC.00741-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Treatment of Experimental Anthrax with Recombinant Capsule Depolymerase{triangledown}

Angelo Scorpio,* Steven A. Tobery, Wilson J. Ribot, and Arthur M. Friedlander*

United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702

Received 7 June 2007/ Returned for modification 9 July 2007/ Accepted 17 December 2007

Bacillus anthracis produces an antiphagocytic gamma-linked poly-D-glutamic acid capsule that is required for virulence. Capsule depolymerase (CapD) is a membrane-associated poly-{gamma}-glutamate-specific depolymerase encoded on the B. anthracis capsule plasmid, pX02, that is reported to contribute to virulence by anchoring the capsule to the peptidoglycan and partially degrading high-molecular-weight capsule from the bacterial surface. We previously demonstrated that treatment with CapD effectively removes the capsule from anthrax bacilli, rendering them susceptible to phagocytic killing in vitro. Here we report that CapD promoted in vivo phagocytic killing of B. anthracis bacilli by mouse peritoneal neutrophils and that parenteral administration of CapD protected mice in two models of anthrax infection. CapD conferred significant protection compared with controls when coinjected with encapsulated bacilli from fully virulent B. anthracis Ames or the nontoxigenic encapsulated strain {Delta}Ames and when injected 10 min after infection with encapsulated bacilli from B. anthracis Ames. Protection was also observed when CapD was administered 30 h after infection with B. anthracis {Delta}Ames spores, while significant protection could not be demonstrated following challenge with B. anthracis Ames spores. These data support the proposed role of capsule in B. anthracis virulence and suggest that strategies to target anthrax bacilli for neutrophil killing may lead to novel postexposure therapies.

* Corresponding author. Mailing address: USAMRIID, 1425 Porter Street, Frederick, MD 21702. Phone for Angelo Scorpio: (301) 619-4935. Fax: (301) 619-2152. E-mail: angelo.scorpio{at}amedd.army.mil. Phone for Arthur M. Friedlander: (301) 619-7343. Fax: (301) 619-2152. E-mail: arthur.friedlander{at}amedd.army.mil

{triangledown} Published ahead of print on 26 December 2007.

Antimicrobial Agents and Chemotherapy, March 2008, p. 1014-1020, Vol. 52, No. 3
0066-4804/08/$08.00+0     doi:10.1128/AAC.00741-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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