Paenibacterin, a novel broad-spectrum lipopeptide antibiotic, neutralises endotoxins and promotes survival in a murine model of Pseudomonas aeruginosa-induced sepsis

Paenibacterin, produced by Paenibacillus thiaminolyticus OSY-SE, is active both against Gram-negative and Gram-positive pathogens, including antibiotic-resistant strains of Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis. Paenibacterin showed relatively low cytotoxicity against a human kidney cell line (ATCC CRL-2190), with a 50% inhibitory concentration (IC50) ≥ 109 μg/mL. The cationic paenibacterin molecule binds to the negatively charged Gram-negative endotoxins in vitro, suggesting that paenibacterin can neutralise lipopolysaccharides. In a murine septic shock model, two 500 μg doses of paenibacterin significantly increased the survival of mice challenged with a lethal level of P. aeruginosa. Considering that paenibacterin is effective against many strains of antibiotic-resistant pathogens, this study suggests that this antimicrobial agent is a promising candidate as a new drug.