The capsule of Bacillus anthracis, a review

Abstract

The capsule of Bacillus anthracis, composed of poly-D-glutamic acid, serves as one of the principal virulence factors during anthrax infection. By virtue of its negative charge, the capsule is purported to inhibit host defence through inhibition of phagocytosis of the vegetative cells by macrophages. In conjunction with lethal toxin and oedema toxin, whose target cells include macrophages and neutrophils, respectively, the capsule allows virulent anthrax bacilli to grow virtually unimpeded in the infected host. Spores germinating in the presence of serum and elevated CO 2 release capsule through openings on the spore surface in the form of blebs which may coalesce before sloughing of the exosporium and outgrowth of the fully encapsulated vegetative cell. It has not been established that spore encapsulation plays a role in the early events of anthrax infection. The capsule appears exterior to the S-layer of the vegetative cell and does not require the S-layer for its attachment to the cell surface. The three membrane-associated enzymes required for synthesis of the capsule are encoded by the 60-MDa pX02 plasmid. The cistrons are arranged in the order capB, capC and capA and encode for proteins of 44, 16 and 46 kDa, respectively. The synthesis of capsule and toxin is, in part, under bicarbonate regulation by interaction of transacting proteins of the atxA gene on the 100-MDa pX01 toxin-encoding plasmid and the acpA gene on the pX02 plasmid. Therefore, capsule synthesis is enhanced in the presence of the atxA gene on the pX01 plasmid. An additional protein (with a predicted size of 51 kDa) is encoded by the dep gene located downstream from the cap region and appears to be a depolymerase that catalyses the hydrolysis of poly-D-glutamic acid into lower molecular weight polyglutamates. Although the biological function of the Dep protein is unknown, it has been proposed that the low molecular weight polyglutamates produced by the action of the enzyme may act to inhibit host defence mechanisms.

Conjugate-like immunogens produced as protein capsular matrix vaccines

“…Preliminary studies in synthesizing and determining the immunogenicity of a PCMV were performed using the T-independent capsular antigen, poly-gamma-D-glutamic acid (PGA), and the carrier/matrix protein DNI, or dominant negative inhibitor, a mutant of the protective antigen (PA) moiety of anthrax toxin (14)(15)(16), derived from B. anthracis. PGA is an atypical capsule in that it is a linear polypeptide generated through gamma peptide bonds of glutamic acid rather than the more common polysaccharide-based capsules (17,18). Furthermore, because PGA is not synthesized from a nucleic acid coding sequence, it is unclear whether this polymer displays an unblocked α-amino group at its N terminus.…”

Common oligosaccharide moieties inhibit the adherence of typical and atypical respiratory pathogens

“…Putative adhesins include the Slayer proteins (EA1 and Sap), teichoic acids, the poly-ª-Dglutamic acid capsule and fibronectin-and collagen-binding proteins (Ariel et al, 2003;Ezzell & Welkos, 1999;Fouet et al, 1999). The carbohydrate specificities displayed in this study (Table 2) were not due to interactions with the capsule, because the strain used lacked the pXO2 plasmid that encodes this virulence factor.…”

Sepsis and Pathophysiology of Anthrax in a Nonhuman Primate Model

“…69 Thus, the study design may not precisely replicate the kinetics of disease progression associated with infection by spores of fully virulent B. anthracis. Additional baboon models are in progress to determine the effect of kinetics on disease development.…”