Metallohelices that kill Gram-negative pathogens using intracellular antimicrobial peptide pathways.

ABSTRACT: A range of new water-compatible optically pure metallohelices - made by self-assembly of simple non-peptidic organic components around Fe ions - exhibit similar architecture to some natural cationic antimicrobial peptides (CAMPs) and are found to have high, structure-dependent activity against bacteria, including clinically problematic Gram-negative pathogens. A key compound is shown to freely enter rapidly dividing E. coli cells without significant membrane disruption, and localise in distinct foci near the poles. Several related observations of CAMP-like mechanisms are made via biophysical measurements, whole genome sequencing of tolerance mutants and transcriptomic analysis. These include: high selectivity for binding of G-quadruplex DNA over double stranded DNA; inhibitio

SUBMITTER: Simpson DH 

PROVIDER: S-EPMC6977464 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature