Serum-mediated cleavage ofBacillus anthracisProtective Antigen is a two-step process that involves a serum carboxypeptidase

Abstract

AbstractMuch our understanding of the activity of anthrax toxin is based onin-vitrosystems, which delineate the interaction betweenB. anthracistoxins and the cell surface. These systems however, fail to account for the intimate association ofB. anthraciswith the circulatory system, including the contribution of serum proteins to the host response and processing of anthrax toxins. Using variety immunologic techniques to inhibit serum processing ofB. anthracisProtective Antigen (PA) along with mass spectrometry analysis, we demonstrate that serum digests PA via 2 distinct reactions. In the first reaction, serum cleaves PA83into 2 fragments to produce PA63and PA20fragments, similar to that observed following furin digestion. This is followed by carboxypeptidase-mediated removal of the carboxy-terminal arginine and lysine residues from PA20.