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

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.


Published in:
Chemical Science, 8, 12, 7991-7997
Year:
2017
Publisher:
Cambridge, Royal Soc Chemistry
ISSN:
2041-6520
Laboratories:




 Record created 2017-12-04, last modified 2018-03-17


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