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.