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

Microbiomes are rife for biotechnological exploitation, particularly the rumen microbiome. In this study, antimicrobial peptides (AMPs) from the rumen microbiome (Lynronne 1, 2, 3 and P15s) were assessed for their therapeutic potential against 7 clinical strains of Pseudomonas aeruginosa. All AMPs exhibited antimicrobial activity against all strains, with minimal inhibitory concentrations (MICs) ranging from 4-512 µg/mL. Time kill kinetics of all AMPs at 4 x MIC values against strains PA01 and LES431 showed complete kill within 10 mins to 4h, although P15s wasn't bactericidal against PA01. All AMPs significantly inhibited biofilm formation by strains PA01 and LES431 and resistance assays showed no decrease in susceptibility against these strains. AMP cytotoxicity against human lung cell lines was also minimal. In terms of mechanism of action, the AMPs showed affinity towards PA01 and LES431 membrane lipids and transcriptome and metabolome analysis showing increased catalytic activity at the cell membrane and promotion of ß-oxidation of fatty acids. Galleria infection models showed that Lynronne 1 and Lynronne 2 were efficacious in vivo, with a 100% survival rate following treatment at MIC concentration. This study illustrates the therapeutic potential of microbiome-derived AMPs P. aeruginosa infections.