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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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Autores principales: McCaughey, Laura C., Ritchie, Neil. D., Douce, Gillian R., Evans, Thomas J., Walker, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957109/
https://www.ncbi.nlm.nih.gov/pubmed/27444885
http://dx.doi.org/10.1038/srep30201
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author McCaughey, Laura C.
Ritchie, Neil. D.
Douce, Gillian R.
Evans, Thomas J.
Walker, Daniel
author_facet McCaughey, Laura C.
Ritchie, Neil. D.
Douce, Gillian R.
Evans, Thomas J.
Walker, Daniel
author_sort McCaughey, Laura C.
collection PubMed
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 pubmed-49571092016-07-26 Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection McCaughey, Laura C. Ritchie, Neil. D. Douce, Gillian R. Evans, Thomas J. Walker, Daniel Sci Rep Article 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. Nature Publishing Group 2016-07-22 /pmc/articles/PMC4957109/ /pubmed/27444885 http://dx.doi.org/10.1038/srep30201 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
McCaughey, Laura C.
Ritchie, Neil. D.
Douce, Gillian R.
Evans, Thomas J.
Walker, Daniel
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957109/
https://www.ncbi.nlm.nih.gov/pubmed/27444885
http://dx.doi.org/10.1038/srep30201
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