An amphipathic peptide with antibiotic activity against multidrug-resistant Gram-negative bacteria.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsElliott, Alysha G
Huang, Johnny X
Edwards, Ingrid A
Cain, Amy K
Boinett, Christine J
Lundberg, Carina Vingsbo
Butler, Mark S
Porter, Kaela M
Blaskovich, Mark A T
Cooper, Matthew A
MetadataShow full item record
AbstractPeptide antibiotics are an abundant and synthetically tractable source of molecular diversity, but they are often cationic and can be cytotoxic, nephrotoxic and/or ototoxic, which has limited their clinical development. Here we report structure-guided optimization of an amphipathic peptide, arenicin-3, originally isolated from the marine lugworm Arenicola marina. The peptide induces bacterial membrane permeability and ATP release, with serial passaging resulting in a mutation in mlaC, a phospholipid transport gene. Structure-based design led to AA139, an antibiotic with broad-spectrum in vitro activity against multidrug-resistant and extensively drug-resistant bacteria, including ESBL, carbapenem- and colistin-resistant clinical isolates. The antibiotic induces a 3–4 log reduction in bacterial burden in mouse models of peritonitis, pneumonia and urinary tract infection. Cytotoxicity and haemolysis of the progenitor peptide is ameliorated with AA139, and the ‘no observable adverse effect level’ (NOAEL) dose in mice is ~10-fold greater than the dose generally required for efficacy in the infection models
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial 4.0 International
- Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert Bactericidal and Therapeutic Activity Against Highly Multidrug-Resistant Gram-Negative Bacterial Pathogens.
- Authors: Lin L, Nonejuie P, Munguia J, Hollands A, Olson J, Dam Q, Kumaraswamy M, Rivera H Jr, Corriden R, Rohde M, Hensler ME, Burkart MD, Pogliano J, Sakoulas G, Nizet V
- Issue date: 2015 Jul
- Cationic amphiphilic alpha-helical peptides for the treatment of carbapenem-resistant Acinetobacter baumannii infection.
- Authors: Huang Y, Wiradharma N, Xu K, Ji Z, Bi S, Li L, Yang YY, Fan W
- Issue date: 2012 Dec
- Investigations into the membrane activity of arenicin antimicrobial peptide AA139.
- Authors: Edwards IA, Henriques ST, Blaskovich MAT, Elliott AG, Cooper MA
- Issue date: 2022 Aug
- Aedesin: structure and antimicrobial activity against multidrug resistant bacterial strains.
- Authors: Godreuil S, Leban N, Padilla A, Hamel R, Luplertlop N, Chauffour A, Vittecoq M, Hoh F, Thomas F, Sougakoff W, Lionne C, Yssel H, Missé D
- Issue date: 2014
- Synergistic effect of antimicrobial peptide arenicin-1 in combination with antibiotics against pathogenic bacteria.
- Authors: Choi H, Lee DG
- Issue date: 2012 Jul