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Antimicrobial Agents and Chemotherapy, January 2007, p. 215-222, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00706-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Poly-{gamma}-Glutamate Capsule-Degrading Enzyme Treatment Enhances Phagocytosis and Killing of Encapsulated Bacillus anthracis{triangledown}

Angelo Scorpio,1* Donald J. Chabot,1 William A. Day,1 David K. O'Brien,1 Nicholas J. Vietri,1 Yoshifumi Itoh,2 Mansour Mohamadzadeh,1 and Arthur M. Friedlander1*

United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702,1 Division of Applied Microbiology, National Food Research Institute, Kannondai 2-1-12, Tsukuba, Ibaraki 305-8642, Japan2

Received 7 June 2006/ Returned for modification 19 July 2006/ Accepted 14 October 2006

The poly-{gamma}-D-glutamic acid capsule confers antiphagocytic properties on Bacillus anthracis and is essential for virulence. In this study, we showed that CapD, a {gamma}-polyglutamic acid depolymerase encoded on the B. anthracis capsule plasmid, degraded purified capsule and removed the capsule from the surface of anthrax bacilli. Treatment with CapD induced macrophage phagocytosis of encapsulated B. anthracis and enabled human neutrophils to kill encapsulated organisms. A second glutamylase, PghP, a {gamma}-polyglutamic acid hydrolase encoded by Bacillus subtilis bacteriophage {Phi}NIT1, had minimal activity in degrading B. anthracis capsule, no effect on macrophage phagocytosis, and only minimal enhancement of neutrophil killing. Thus, the levels of both phagocytosis and killing corresponded to the degree of enzyme-mediated capsule degradation. The use of enzymes to degrade the capsule and enable phagocytic killing of B. anthracis offers a new approach to the therapy of anthrax.

* Corresponding author. Mailing address: USAMRIID, 1425 Porter Street, Frederick, MD 21702. Phone for Angelo Scorpio: (301) 619-4935. Fax: (301) 619-4299. E-mail: Angelo.Scorpio{at}amedd.army.mil. Phone for Arthur M. Friedlander: (301) 619-7343. Fax: (301) 619-4299. E-mail: Arthur.Friedlander{at}amedd.army.mil.

{triangledown} Published ahead of print on 30 October 2006.

Antimicrobial Agents and Chemotherapy, January 2007, p. 215-222, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00706-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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