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

Autor: Mulkern AJ; IBERS, Aberystwyth University, Aberystwyth, SY23 3DA, Wales, UK. mulkern.adam@mh-hannover.de.; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany. mulkern.adam@mh-hannover.de., Oyama LB; Institute for Global Food Security, 19 Chlorine Gardens, Queen's University of Belfast, Belfast, Northern Ireland, BT9 5DP, UK., Cookson AR; IBERS, Aberystwyth University, Aberystwyth, SY23 3DA, Wales, UK., Creevey CJ; Institute for Global Food Security, 19 Chlorine Gardens, Queen's University of Belfast, Belfast, Northern Ireland, BT9 5DP, UK., Wilkinson TJ; IBERS, Aberystwyth University, Aberystwyth, SY23 3DA, Wales, UK.; The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Roslin, Edinburgh, EH25 9RG, UK., Olleik H; Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, 13397, Marseille, France., Maresca M; Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, 13397, Marseille, France., da Silva GC; Laboratório de Genética Molecular de Bactérias, Departamento de Microbiologia, Instituto de Biotecnologia Aplicada à Agropecuária, Universidade Federal de Viçosa, Viçosa, Brazil., Fontes PP; Laboratório de Genética Molecular de Bactérias, Departamento de Microbiologia, Instituto de Biotecnologia Aplicada à Agropecuária, Universidade Federal de Viçosa, Viçosa, Brazil., Bazzolli DMS; Laboratório de Genética Molecular de Bactérias, Departamento de Microbiologia, Instituto de Biotecnologia Aplicada à Agropecuária, Universidade Federal de Viçosa, Viçosa, Brazil., Mantovani HC; Departamento de Microbiologia, Universidade Federal de Viçosa, Viçosa, 36570-900, Brazil., Damaris BF; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany., Mur LAJ; IBERS, Aberystwyth University, Aberystwyth, SY23 3DA, Wales, UK., Huws SA; Institute for Global Food Security, 19 Chlorine Gardens, Queen's University of Belfast, Belfast, Northern Ireland, BT9 5DP, UK. s.huws@qub.ac.uk.
Jazyk: angličtina
Zdroj: NPJ biofilms and microbiomes [NPJ Biofilms Microbiomes] 2022 Aug 29; Vol. 8 (1), pp. 70. Date of Electronic Publication: 2022 Aug 29.
DOI: 10.1038/s41522-022-00332-w
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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