Engineered alpha-defensin peptides display antimicrobial activity against oral pathogens

Introduction: Human alpha defensins are a family of neutrophil-derived antimicrobial peptides also known as human neutrophil peptides (HNPs). The defensin family of peptides are characterised by six invariant cysteine residues forming three disulphide bridges. The formation of the correct disulphide pairs complicates the synthesis of full length human alpha defensin and limits its therapeutic potential as an antimicrobial peptide. Objectives: The aim of this study was to determine whether truncated alpha defensins displayed antimicrobial activity against a range of micro-organisms including oral pathogens. Methods: Engineered peptides were synthesised by solid-phase methods using standard Fmoc chemistry. Antibacterial assays were performed using a previously described ultra sensitive radial diffusion method. A total of five engineered defensin peptides and full length alpha defensin were tested for their sensitivity against eight micro-organisms, including Gram negative bacteria, Gram positive bacteria and fungal pathogens Results: Antimicrobial activity was identified as clear zones around peptide-containing wells. Zone diameters were used to calculate minimum inhibitory concentrations (MICs) for each peptide. There was considerable variability in the susceptibility of the micro-organisms to the truncated analogues. Bacillus subtilis and Enterococcus faecalis were sensitive to the majority of the engineered peptides whereas Staphylococcus aureus, Escherichia coli and Candida albicans displayed resistance (defined as an MIC of greater than 250 ug/ml) to the truncated defensins. Of the five engineered peptides synthesised, the 2-aminobenzoic acid (Abz)-containing analogues based on the C-terminal sequence of alpha defensin displayed MIC values closest to that of the full length defensin in 5 out of 8 micro-organisms studied. Conclusion: This study demonstrates that truncated alpha defensins display variable antimicrobial activity against a range of micro-organisms, including oral pathogens. The generation of truncated defensins without disulphide bridges simplifies their synthesis and increases their therapeutic potential.

Display At Your Own Risk: An experimental exhibition of digital cultural heritage

Display At Your Own Risk is a research-led exhibition experiment concerned with the use and reuse of digital surrogates of public domain works of art produced by cultural heritage institutions of international repute. This publication is issued in conjunction with the open source exhibition, available at: displayatyourownrisk.org.

Display At Your Own Risk: The Metadata

This book contains the Exif, XMP, and IPTC metadata extract ed from the 100 digital surrogates featured in Display At Your Own Risk, an online exhibition experiment. In some cases, the metadata is extensive, almost overwhelming; in others, little to no metadata was embedded in the digital surrogate's file at all. Preparing this book to accompany the Display At Your Own Risk exhibition made us realise that metadata can be beautiful. We hope you find beauty here too.

Display At Your Own Risk

Display At Your Own Risk (DAYOR) is a research-led exhibition experiment featuring digital surrogates of public domain works of art produced by cultural heritage institutions of international repute. The project includes a gallery exhibition, an open source version of that exhibition intended for public use, and two online publications: the Exhibition Catalogue, and a companion Metadata Book.