Redirecting Pseudomonas exotoxin

Abstract

Pseudomonas exotoxin (PE) is a three-domain bacterial toxin that kills mammalian cells by gaining entry to the cytosol and inactivating protein synthesis. The pathway of toxin entry includes binding to a surface receptor, internalization via coated pits and endosomes, proteolytic processing, reduction of disulfide bonds and finally the translocation of an enzymatically active C-terminal fragment to the cytosol. Once in the cytosol this fragment inhibits protein synthesis by ADP ribosylating elongation factor 2. Because of its potency PE and its derivatives have been directed to kill various target cells. It is hoped this strategy will lead to the development of a novel kind of therapeutic agent for the treatment of various human diseases including cancer, AIDS and various immunological disorders.