Files and links (1)
Published (Version of record)CC BY V4.0, Open Access
Journal article
Self-assembling dipeptide antibacterial nanostructures with membrane disrupting activity
Nature Communications, Vol.8, 1365
08/Nov/2017
Abstract
Peptide-based supramolecular assemblies are a promising class of nanomaterials with important biomedical applications, specifically in drug delivery and tissue regeneration. However, the intrinsic antibacterial capabilities of these assemblies have been largely overlooked. The recent identification of common characteristics shared by antibacterial and self-assembling peptides provides a paradigm shift towards development of antibacterial agents. Here we present the antibacterial activity of self-assembled diphenylalanine, which emerges as the minimal model for antibacterial supramolecular polymers. The diphenylalanine nano-assemblies completely inhibit bacterial growth, trigger upregulation of stress-response regulons, induce substantial disruption to bacterial morphology, and cause membrane permeation and depolarization. We demonstrate the specificity of these membrane interactions and the development of antibacterial materials by integration of the peptide assemblies into tissue scaffolds. This study provides important insights into the significance of the interplay between self-assembly and antimicrobial activity and establishes innovative design principles toward the development of antimicrobial agents and materials.
Details
- Title
- Self-assembling dipeptide antibacterial nanostructures with membrane disrupting activity
- Creators
- Lee Schnaider (null)Sayanti Brahmachari (null)Nathan W. Schmidt (null)Bruk Mensa (null)Shira Shaham-Niv (null)Darya Bychenko (null)Lihi Adler-Abramovich (null)Linda J. W. Shimon (null) - 972WIS_INST___100Sofiya Kolusheva (null)William F. DeGrado (Corresponding Author)Ehud Gazit (Corresponding Author)
- Resource Type
- Journal article
- Publication Details
- Nature Communications, Vol.8, 1365; 08/Nov/2017
- Number of pages
- 10
- Language
- English
- DOI
- https://doi.org/10.1038/s41467-017-01447-x
- Grant note
- We thank Yael Diesendruck for her guidance and thoughtful insights throughout the project; Zohar A. Arnon for his valuable assistance in figure preparation; Dr Vered Holdengreber for her helpful assistance in preparation of bacterial samples for electron microscopy; and Professor Oren Regev and Dr Einat Nativ-Roth for their valuable assistance in high-resolution transmitting electron microscopy analysis. We thank Professor Anat Herskovits, Professor Eliora Ron, and Dr Dvora Biran for the generosity in providing the Listeria and Rhizobium bacterial strains. We thank Tom Guterman and the members of the Gazit group for fruitful discussions. This research was supported by the Israeli Ministry of Science, Technology and Space (L.S.). Author contributions L.S., L.A.-A., W.F.D. and E.G. conceived and designed the experiments. L.S. planned and performed or participated in all experiments. S.B. prepared and analyzed the antimicrobial tissue scaffolds and performed SEM and circular dichroism analyses. N.W.S. performed the analysis of the upregulation of gene expression, and N.W.S. and B.M. constructed the plasmid reporters used in these experiments. S.S.-N. performed the MTT cell viability analysis. D.B. performed antibacterial analyses. S.K. prepared the liposomal model membrane systems performed these experiments. L.J.W.S. participated in the structural analysis. L.S., W.F.D. and E.G. wrote the paper. All authors discussed the results and commented on the manuscript.
- Record Identifier
- 993261963603596
Metrics
4 Record Views