Microbiome-derived antimicrobial peptides offer therapeutic solutions for the treatment of Pseudomonas aeruginosa infections

AJ Mulkern, LB Oyama, AR Cookson, CJ Creevey, TJ Wilkinson, H Olleik, M Maresca, GC da Silva, PP Fontes, DMS Bazzolli, HC Mantovani, BF Damaris, LAJ Mur, SA Huws

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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 languageEnglish
Article number70
Number of pages15
Journalnpj Biofilms and Microbiomes
Issue number1
Early online date29 Aug 2022
Publication statusPublished - 01 Dec 2022


  • Antimicrobial Cationic Peptides/pharmacology
  • Microbiota
  • Animals
  • Humans
  • Pseudomonas aeruginosa
  • Pseudomonas Infections/drug therapy
  • Antimicrobial Peptides


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