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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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/srep30201

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
ORCID:
0000-0001-5897-0163
More by this author
Role:
Author
ORCID:
0000-0002-6654-7346
More by this author
Role:
Author
ORCID:
0000-0002-4206-2942


Publisher:
Springer Nature
Journal:
Scientific Reports More from this journal
Volume:
6
Issue:
1
Article number:
30201
Place of publication:
England
Publication date:
2016-07-22
Acceptance date:
2016-06-30
DOI:
EISSN:
2045-2322
ISSN:
2045-2322
Pmid:
27444885


Language:
English
Pubs id:
638258
Local pid:
pubs:638258
Deposit date:
2020-06-12

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