title: Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection.
abstract: Protein antibiotics, known as bacteriocins, are widely produced by bacteria for intraspecies competition. The potency and targeted action of bacteriocins suggests that they could be developed into clinically useful antibiotics against highly drug resistant Gram-negative pathogens for which there are few therapeutic options. Here we show that Pseudomonas aeruginosa specific bacteriocins, known as pyocins, show strong efficacy in a murine model of P. aeruginosa lung infection, with the concentration of pyocin S5 required to afford protection from a lethal infection at least 100-fold lower than the most commonly used inhaled antibiotic tobramycin. Additionally, pyocins are stable in the lung, poorly immunogenic at high concentrations and efficacy is maintained in the presence of pyocin specific antibodies after repeated pyocin administration. Bacteriocin encoding genes are frequently found in microbial genomes and could therefore offer a ready supply of highly targeted and potent antibiotics active against problematic Gram-negative pathogens.
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.|The ithree institute, University of Technology Sydney, Ultimo, New South Wales, Australia.|Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK.
authors.forename: Laura C
authors.initials: LC
authors.lastname: McCaughey
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Ritchie
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
authors.forename: Gillian R
authors.initials: GR
authors.lastname: Douce
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Evans
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Walker
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001430:Bacteriocins / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000382:microbiology*; D008171:Lung Diseases / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011709:Pyocins / Q000494:pharmacology; D013045:Species Specificity; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D011709:Pyocins; D014031:Tobramycin