Poly-gamma-glutamate capsule-degrading enzyme treatment enhances phagocytosis and killing of encapsulated Bacillus anthracis.
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 PhiNIT1, 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.
Scorpio
Angelo
A
USAMRIID, 1425 Porter Street, Frederick, MD 21702, USA. Angelo.Scorpio@amedd.army.mil
Chabot
Donald J
DJ
Day
William A
WA
O'brien
David K
DK
Vietri
Nicholas J
NJ
Itoh
Yoshifumi
Y
Mohamadzadeh
Mansour
M
Friedlander
Arthur M
AM
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001408:Bacillus anthracis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001412:Bacillus subtilis / Q000187:drug effects / Q000378:metabolism; D016667:Bacterial Capsules / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D011099:Polyglutamic Acid / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D011623:gamma-Glutamyl Hydrolase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D011994:Recombinant Proteins; C030325:anthrax toxin; D011099:Polyglutamic Acid; D005723:gamma-Glutamyltransferase; D011623:gamma-Glutamyl Hydrolase