Projects per year
Abstract
Microbiomes are rife for biotechnological exploitation, particularly the rumen microbiome, due to their complexicity and diversity. In this study, antimicrobial peptides (AMPs) from the rumen microbiome (Lynronne 1, 2, 3 and P15s) were assessed for their therapeutic potential against seven clinical strains of Pseudomonas aeruginosa. All AMPs exhibited antimicrobial activity against all strains, with minimum inhibitory concentrations (MICs) ranging from 4–512 µg/mL. Time-kill kinetics of all AMPs at 3× MIC values against strains PAO1 and LES431 showed complete kill within 10 min to 4 h, although P15s was not bactericidal against PAO1. All AMPs significantly inhibited biofilm formation by strains PAO1 and LES431, and induction of resistance assays showed no decrease in activity against these strains. AMP cytotoxicity against human lung cells was also minimal. In terms of mechanism of action, the AMPs showed affinity towards PAO1 and LES431 bacterial membrane lipids, efficiently permeabilising the P. aeruginosa membrane. Transcriptome and metabolome analysis revealed increased catalytic activity at the cell membrane and promotion of β-oxidation of fatty acids. Finally, tests performed with the Galleria mellonella infection model showed that Lynronne 1 and 2 were efficacious in vivo, with a 100% survival rate following treatment at 32 mg/kg and 128 mg/kg, respectively. This study illustrates the therapeutic potential of microbiome-derived AMPs against P. aeruginosa infections.
Original language | English |
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Article number | 70 |
Number of pages | 15 |
Journal | npj Biofilms and Microbiomes |
Volume | 8 |
Issue number | 1 |
Early online date | 29 Aug 2022 |
DOIs | |
Publication status | Published - 01 Dec 2022 |
Keywords
- GALLERIA-MELLONELLA
- BIOFILMS
- RESISTANCE
- ARGININE
- ROLES
- Antimicrobial Cationic Peptides/pharmacology
- Microbiota
- Animals
- Humans
- Pseudomonas aeruginosa
- Pseudomonas Infections/drug therapy
- Antimicrobial Peptides
Fingerprint
Dive into the research topics of 'Microbiome-derived antimicrobial peptides offer therapeutic solutions for the treatment of Pseudomonas aeruginosa infections'. Together they form a unique fingerprint.Projects
- 2 Finished
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Prospecting the rumen ecosystem for novel antimicrobials for animal and human health- INSTITUTIONAL LINKS
Huws, S. (PI)
01 Apr 2015 → 31 Mar 2017
Project: Externally funded research
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Characterisation and exploitation of novel antimicrobials within the rumen microbiota
Huws, S. (PI), Creevey, C. (CoI), Kingston-Smith, A. (CoI), McEwan, N. (CoI) & Newbold, J. (CoI)
Biotechnology and Biological Sciences Research Council
01 Apr 2014 → 31 Mar 2018
Project: Externally funded research
Equipment
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Genome sequencer [HiSeq 2500]
Darby, R. (Manager)
Institute of Biological, Environmental & Rural Sciences (IBERS)Facility/equipment: Equipment