Poly-γ-Glutamate Capsule-Degrading Enzyme Treatment Enhances Phagocytosis and Killing of Encapsulated Bacillus anthracis
Abstract
Poly-γ-Glutamate Capsule-Degrading Enzyme Treatment Enhances Phagocytosis and Killing of Encapsulated Bacillus anthracis ▿ 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. Friedlander 1 , * 1 United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702 2 Division of Applied Microbiology, National Food Research Institute, Kannondai 2-1-12, Tsukuba, Ibaraki 305-8642, Japan ABSTRACT The poly-γ- d -glutamic acid capsule confers antiphagocytic properties on Bacillus anthracis and is essential for virulence. In this study, we showed that CapD, a γ-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 γ-polyglutamic acid hydrolase encoded by Bacillus subtilis bacteriophage ΦNIT1, 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.