Pyocin efficacy in a murine model of Pseudomonas aeruginosa sepsis

Six, A., Mosbahi, K., Barge, M., Kleanthous, C., Evans, T. and Walker, D. (2021) Pyocin efficacy in a murine model of Pseudomonas aeruginosa sepsis. Journal of Antimicrobial Chemotherapy, 76(9), pp. 2317-2324. (doi: 10.1093/jac/dkab199) (PMID:34142136) (PMCID:PMC8361349)

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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 < 0.05). 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Walker, Professor Daniel and Evans, Professor Tom and Barge, Dr Madhuri and Six, Dr Anne and Mosbahi, Dr Khedidja
Authors: Six, A., Mosbahi, K., Barge, M., Kleanthous, C., Evans, T., and Walker, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Antimicrobial Chemotherapy
Publisher:Oxford University Press
ISSN:0305-7453
ISSN (Online):1460-2091
Published Online:18 June 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Journal of Antimicrobial Chemotherapy 76(9): 2317-2324
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173241Protein Antibiotics: Discovery, mode of action and developmentDaniel WalkerWellcome Trust (WELLCOTR)ALR01040 / 201505/Z/16/ZIII - Bacteriology
306054Confidence in Concept 2019Anna DominiczakMedical Research Council (MRC)MC_PC_18048MVLS - College Senior Management
306935Targeted antibiotic therapy for highly drug-resistant lung infections in cystic fibrosisKhedidja MosbahiTenovus Scotland (TENOVUS)S19-04III - Bacteriology