The Furin Inhibitor Hexa-d-Arginine Blocks the Activation of Pseudomonas aeruginosa Exotoxin A In Vivo

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.