Issue 12, 2017

De novo identification of lipid II binding lipopeptides with antibacterial activity against vancomycin-resistant bacteria

Abstract

Creative strategies for identifying new antibiotics are essential to addressing the looming threat of a post-antibiotic era. We here report the use of a targeted peptide phage display screen as a means of generating novel antimicrobial lipopeptides. Specifically, a library of phage displayed bicyclic peptides was screened against a biomolecular target based on the bacterial cell wall precursor lipid II. In doing so we identified unique lipid II binding peptides that upon lipidation were found to be active against a range of Gram-positive bacteria including clinically relevant strains of vancomycin resistant bacteria. Optimization of the peptide sequence led to variants with enhanced antibacterial activity and reduced hemolytic activity. Biochemical experiments further confirm a lipid II mediated mode of action for these new-to-nature antibacterial lipopeptides.

Graphical abstract: De novo identification of lipid II binding lipopeptides with antibacterial activity against vancomycin-resistant bacteria

Supplementary files

Article information

Article type
Edge Article
Submitted
04 Aug 2017
Accepted
29 Sep 2017
First published
02 Oct 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 7991-7997

De novo identification of lipid II binding lipopeptides with antibacterial activity against vancomycin-resistant bacteria

P. 't Hart, T. M. Wood, K. H. M. E. Tehrani, R. M. van Harten, M. Śleszyńska, I. Rentero Rebollo, A. P. A. Hendrickx, R. J. L. Willems, E. Breukink and N. I. Martin, Chem. Sci., 2017, 8, 7991 DOI: 10.1039/C7SC03413J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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