Anthrax Toxin Edema Factor: A Bacterial Adenylate Cyclase Which Acts within Eukaryotic Cells

摘要

Anthrax toxin is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins individually cause no known physiological effects in animals, but when combined pairwise produce two toxic actions. Injection of PA together with LF causes death of rats in 60 min, while PA combined with EF causes edema in the skin of rabbits and guinea pigs. The mechanisms of action of these proteins have not previously been determined. It is shown here that EF is an adenylate cyclase produced by Bacillus anthracis in an inactive form. Edema factor enters eukaryotic cells in a process mediated by and totally dependent on PA, which appears to bind to cells so as to form an uptake mechanism that can be used by either LF or EF. Edema factor becomes activated inside cells upon contact with an unidentified, heat-stable eukaryotic cell material.