Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection

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...

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Main Authors: McCaughey, LC, Ritchie, ND, Douce, GR, Evans, TJ, Walker, D
Format: Journal article
Language:English
Published: Springer Nature 2016
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author McCaughey, LC
Ritchie, ND
Douce, GR
Evans, TJ
Walker, D
author_facet McCaughey, LC
Ritchie, ND
Douce, GR
Evans, TJ
Walker, D
author_sort McCaughey, LC
collection OXFORD
description 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.
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spelling oxford-uuid:2bc1c02d-294d-46c8-99f6-98addd7de75c2022-03-26T12:32:51ZEfficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2bc1c02d-294d-46c8-99f6-98addd7de75cEnglishSymplectic ElementsSpringer Nature2016McCaughey, LCRitchie, NDDouce, GREvans, TJWalker, DProtein 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.
spellingShingle McCaughey, LC
Ritchie, ND
Douce, GR
Evans, TJ
Walker, D
Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection
title Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection
title_full Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection
title_fullStr Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection
title_full_unstemmed Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection
title_short Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection
title_sort efficacy of species specific protein antibiotics in a murine model of acute pseudomonas aeruginosa lung infection
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