title: Paenibacterin, a novel broad-spectrum lipopeptide antibiotic, neutralises endotoxins and promotes survival in a murine model of Pseudomonas aeruginosa-induced sepsis.
abstract: 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)≥109μg/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 500μg 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.
authors.affiliation: Department of Food Science and Technology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: En
authors.initials: E
authors.lastname: Huang
authors.affiliation: Department of Food Science and Technology, The Ohio State University, Columbus, OH 43210, USA; Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA. Electronic address: yousef.1@osu.edu.
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Yousef
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D004731:Endotoxins; D055666:Lipopeptides; C577323:paenibacterin
keywords: Antibiotic resistance; Endotoxin; Lipopeptide antibiotic; Paenibacterin; Pseudomonas aeruginosa