In situ nanoscale imaging reveals self-concentrating nanomolar antimicrobial pores

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.