High therapeutic index of factor C Sushi peptides: Potent antimicrobials against Pseudomonas aeruginosa

Factor C protein isolated from the horseshoe crab, Carcinoscorpius rotundic auda, has endotoxin binding capability. Synthetic peptides of 34 amino acid s 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 clinic al isolates of Pseudomonas aeruginosa. Collectively, all four peptides demo nstrated exceptionally effective bactericidal activity against P. aeruginos a with 90% minimal bactericidal concentrations (MBC(90)s) in the range of 0 .06 to 0.25 mug/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 conc entrations up to 1,600-fold their MBC(90)s. Both in vitro and in vivo studi es indicate that cytotoxic effects are small even at 1,000-fold their MBC(9 0)s. Furthermore, the Sushi peptides are tolerant of high-salt and adverse pH conditions. These findings demonstrate the promising therapeutic potenti al of the Sushi peptides.