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

McCaughey, L. C., Ritchie, N. D., Douce, G. R. , Evans, T. J. and Walker, D. (2016) Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection. Scientific Reports, 6, 30201. (doi:10.1038/srep30201) (PMID:27444885) (PMCID:PMC4957109)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Walker, Professor Daniel and Evans, Professor Tom and Ritchie, Dr Neil and Mccaughey, Miss Laura and Douce, Dr Gillian
Authors: McCaughey, L. C., Ritchie, N. D., Douce, G. R., Evans, T. J., and Walker, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Published Online:21 July 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Scientific Reports 6:30201
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
558551Development of pyocins active against Pseudomonas aeruginosaDaniel WalkerWellcome Trust (WELLCOME)093592/Z/10/ZIII - BACTERIOLOGY
660151Priming Innovative Translational Research - The University of Glasgow Confidence in Concept ProgrammeAnna DominiczakMedical Research Council (MRC)MC_PC_13063RI CARDIOVASCULAR & MEDICAL SCIENCES