High Therapeutic Index of Factor C Sushi Peptides: Potent Antimicrobials against Pseudomonas aeruginosa

Abstract

ABSTRACT Factor C protein isolated from the horseshoe crab, Carcinoscorpius rotundicauda , has endotoxin binding capability. Synthetic peptides of 34 amino acids based on the sequence of two regions of factor C (Sushi 1 and Sushi 3) as well as their corresponding mutants exhibited activities against 30 clinical isolates of Pseudomonas aeruginosa . Collectively, all four peptides demonstrated exceptionally effective bactericidal activity against P. aeruginosa with 90% minimal bactericidal concentrations (MBC 90 s) in the range of 0.06 to 0.25 μg/ml (16 to 63 nM). Viable bacteria were reduced by 90% after 7 min and were totally eradicated within 40 to 50 min. These peptides are minimally hemolytic against both rabbit and human erythrocytes even at concentrations up to 1,600-fold their MBC 90 s. Both in vitro and in vivo studies indicate that cytotoxic effects are small even at 1,000-fold their MBC 90 s. Furthermore, the Sushi peptides are tolerant of high-salt and adverse pH conditions. These findings demonstrate the promising therapeutic potential of the Sushi peptides.