Microbiome-derived antimicrobial peptides show therapeutic activity against the critically important priority pathogen, Acinetobacter baumannii.

Autor: Alexander PJ; Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, UK., Oyama LB; Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, UK., Olleik H; Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 (UMR7313), Marseille, France., Godoy Santos F; Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, UK., O'Brien S; School of Pharmacy, QUB, Medical Biology Centre, Belfast, UK., Cookson A; Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, UK., Cochrane SA; School of Chemistry and Chemical Engineering, Queen's University Belfast, Belfast, UK., Gilmore BF; School of Pharmacy, QUB, Medical Biology Centre, Belfast, UK., Maresca M; Aix Marseille Univ, CNRS, Centrale Marseille, iSm2 (UMR7313), Marseille, France., Huws SA; Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, UK. s.huws@qub.ac.uk.
Jazyk: angličtina
Zdroj: NPJ biofilms and microbiomes [NPJ Biofilms Microbiomes] 2024 Sep 30; Vol. 10 (1), pp. 92. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1038/s41522-024-00560-2
Abstrakt: Acinetobacter baumannii is designated by the World Health Organisation as a critical priority pathogen. Previously we discovered antimicrobial peptides (AMPs), namely Lynronne-1, -2 and -3, with efficacy against bacterial pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa. Here we assessed Lynronne-1, -2 and -3 structure by circular dichroism and efficacy against clinical strains of A. baumannii. All Lynronne AMPs demonstrated alpha-helical secondary structures and had antimicrobial activity towards all tested strains of A. baumannii (Minimum Inhibitory Concentrations 2-128 μg/ml), whilst also having anti-biofilm activity. Lynronne-2 and -3 demonstrated additive effects with amoxicillin and erythromycin, and synergy with gentamicin. The AMPs demonstrated little toxicity towards mammalian cell lines or Galleria mellonella. Fluorescence-based assay data demonstrated that Lynronne-1 and -3 had higher membrane-destabilising action against A. baumannii in comparison with Lynronne-2, which was corroborated by transcriptomic analysis. For the first time, we demonstrate the therapeutic activity of Lynronne AMPs against A. baumannii.
(© 2024. The Author(s).)
Databáze: MEDLINE
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