In situ nanoscale imaging reveals self-concentrating nanomolar antimicrobial pores. Issue 24 (16th May 2022)

• Record Type: Journal Article
• Authors: Hammond, Katharine; Moffat, Jonathan; Mulcahy, Chris; Hoogenboom, Bart W.; Ryadnov, Maxim G.
• Is Part Of: Nanoscale. Volume 14:Issue 24(2022)
• Page Start: 8586
• Page End: 8593
• Publication Date: 2022-05-16
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d2nr00434h
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : Bacteriocins self-concentrate in bacterial membranes and porate them at nanomolar concentrations. Abstract : Host defence peptides are critical factors of immune systems in all life forms. Considered for therapeutic development in the post-antibiotic era, these molecules rupture microbial membranes at micromolar concentrations. Here we report a self-concentrating mechanism of membrane disruption, which occurs at therapeutically more relevant nanomolar concentrations. Induced by a four-helix bacteriocin the mechanism manifests in a multi-modal disruption pattern. Using in situ atomic force microscopy we show that the pattern and its kinetic profiles remain the same in a range of nano-to-micromolar concentrations. We reveal that the bacteriocin creates its own boundaries in phospholipid bilayers in which it self-concentrates to promote transmembrane poration. The findings offer an exploitable insight into nanomolar antimicrobial mechanisms.