Pyocin efficacy in a murine model of Pseudomonas aeruginosa sepsis

Six, Anne and Mosbahi, Khedidja and Barge, Madhuri and Kleanthous, Colin and Evans, Thomas and Walker, Daniel (2021) Pyocin efficacy in a murine model of Pseudomonas aeruginosa sepsis. Journal of Antimicrobial Chemotherapy, 76 (9). 2317–2324. ISSN 0305-7453 (https://doi.org/10.1093/jac/dkab199)

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Abstract

Background: Bloodstream infections with antibiotic-resistant Pseudomonas aeruginosa are common and increasingly difficult to treat. Pyocins are naturally occurring protein antibiotics produced by P. aeruginosa that have potential for human use. Objectives: To determine if pyocin treatment is effective in a murine model of sepsis with P. aeruginosa. Methods: Recombinant pyocins S5 and AP41 were purified and tested for efficacy in a Galleria mellonella infection model and a murine model of P. aeruginosa sepsis. Results: Both pyocins produced no adverse effects when injected alone into mice and showed good in vitro antipseudomonal activity. In an invertebrate model of sepsis using G. mellonella, both pyocins significantly prolonged survival from 1/10 (10%) survival in controls to 80%–100% survival among groups of 10 pyocin-treated larvae. Following injection into mice, both showed extensive distribution into different organs. When administered 5 h after infection, pyocin S5 significantly increased survival from 33% (2/6) to 83% (5/6) in a murine model of sepsis (difference significant by log-rank test, P  Conclusions: Pyocins S5 and AP41 show in vivo biological activity and can improve survival in two models of P. aeruginosa infection. They hold promise as novel antimicrobial agents for treatment of MDR infections with this microbe.

ORCID iDs

Six, Anne, Mosbahi, Khedidja, Barge, Madhuri, Kleanthous, Colin, Evans, Thomas and Walker, Daniel ORCID logoORCID: https://orcid.org/0000-0002-4206-2942;
  • Item type:Article
    ID code:86203
    Dates:
    Date
    Event
    12 August 2021
    Published
    20 May 2021
    Accepted
    4 November 2020
    Submitted
    Notes:Anne Six and others, Pyocin efficacy in a murine model of Pseudomonas aeruginosa sepsis, Journal of Antimicrobial Chemotherapy, Volume 76, Issue 9, September 2021, Pages 2317–2324, https:// doi.org/10.1093/jac/dkab199 © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
    Subjects:Medicine > Pharmacy and materia medica
    Science > Microbiology
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:20 Jul 2023 12:16
    Last modified:11 Nov 2024 14:00
    URI:https://strathprints.strath.ac.uk/id/eprint/86203
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