The Furin Inhibitor Hexa-<scp>d</scp>-Arginine Blocks the Activation of<i>Pseudomonas aeruginosa</i>Exotoxin A In Vivo

Abstract

The Pseudomonas aeruginosa exotoxin A (PEA) protein requires furin-mediated cleavage for manifestation of toxicity. We show here that the small stable furin inhibitor hexa-D-arginine amide effectively blocks PEA-induced cell lysis and is itself noncytotoxic. Administration of hexa-D-arginine to PEA-treated mice significantly improves their survival rate and also decreases circulating levels of tumor necrosis factor alpha.