Hammond, K; Moffat, J; Mulcahy, C; Hoogenboom, B W; Ryadnov, M G (2022) In situ nanoscale imaging reveals self-concentrating nanomolar antimicrobial pores. Nanoscale, 14 (24). pp. 8586-8593.

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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 video-rate 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.

Item Type:	Article
Subjects:	Biotechnology > Biopharmaceutical Manufacturing and Characterisation
Divisions:	Chemical & Biological Sciences
Identification number/DOI:	10.1039/d2nr00434h
Last Modified:	27 Jul 2022 14:09
URI:	https://eprintspublications.npl.co.uk/id/eprint/9504