Serum-mediated cleavage of Bacillus anthracis Protective Antigen is a two-step process that involves a serum carboxypeptidase

David L. Goldman, Edward Nieves, Antonio Nakouzi, Johanna Rivera, Ei Ei Phyu, Than Htut Win, Jacqueline Achkar, Arturo Casadevall

Research output: Contribution to journalArticlepeer-review

Abstract

Much our understanding of the activity of anthrax toxin is based on in-vitro systems, which delineate the interaction between B. anthracis toxins and the cell surface. These systems however, fail to account for the intimate association of B. anthracis with 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 of B. anthracis Protective Antigen (PA) along with mass spectrometry analysis, we demonstrate that serum digests PA via 2 distinct reactions. In the first reaction, serum cleaves PA83 into 2 fragments to produce PA63 and PA20 fragments, similar to that observed following furin digestion. This is followed by carboxypeptidase-mediated removal of the carboxy-terminal arginine and lysine residues from PA20.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Feb 18 2018
Externally publishedYes

Keywords

  • anthrax
  • innate immunity
  • lethal toxin
  • protease
  • serum

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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