Abstract
Biofilms present a major problem to industry and healthcare worldwide. Composed of a population of surface-attached microbial cells surrounded by a protective extracellular polysaccharide matrix, they are responsible for increased tolerance to antibiotics, treatment failure and a resulting rise in antimicrobial resistance. Here we demonstrate that self assembled peptide nanostructures composed of a diphenylalanine motif provide sufficient antibacterial activity to eradicate mature biofilm forms of bacteria widely implicated in hospital infections. Modification of terminal functional groups to amino (-NH2), carboxylic acid(-COOH) or both modalities, and switch to d-isomers, resulted in changes in antibacterial selectivity and mammalian cell toxicity profiles. Of the three peptide nanotubes structures studied (NH2-FF-COOH, NH2-ff-COOH and NH2-FF-NH2), NH2-FF-COOH demonstrated themost potent activity against both planktonic (liquid, free-floating) and biofilm forms of bacteria, possessing minimal mammalian cell toxicity. NH2-FF-COOH resulted in greater than 3 Log10 CFU/mL viable biofilm reduction (>99.9%) at 5 mg/mL and total biofilm kill at 10mg/mL against Staphylococcus aureus after 24 hours exposure. Scanning electron microscopy proved that antibiofilm activity was primarily due to the formation of ion channels and/or surfactant-like action, with NH2-FF-COOH and NH2-ff-COOH capable of degrading the biofilm matrix and disrupting cell membranes, leading to cell death in Gram-positive bacterial isolates. Peptide-based nanotubes are an exciting platform for drug delivery and engineering applications. This is the first report of using peptide nanotubes to eradicate bacterial biofilms and provides evidence of a new platform that may alleviate their negative impact throughout society
Original language | English |
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Pages (from-to) | 96-105 |
Number of pages | 10 |
Journal | Acta Biomaterialia |
Volume | 77 |
Early online date | 19 Jul 2018 |
DOIs | |
Publication status | Published - Sep 2018 |
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Student Theses
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Peptide-mimetic hydrogels as a long-acting drug delivery platform for HIV/AIDS
Author: Coulter, S., Jul 2020Supervisor: Laverty, G. (Supervisor) & Malcolm, K. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy
Profiles
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Garry Laverty
- School of Pharmacy - Senior Lecturer
- Material and Advanced Technologies for Healthcare
Person: Academic