Flowering Poration-A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold

Katharine Hammond; Helen Lewis; Samantha Halliwell; Florie Desriac; Brunello Nardone; Jascindra Ravi; Bart W Hoogenboom; Mathew Upton; Jeremy P Derrick; Maxim G Ryadnov

doi:10.1016/j.isci.2020.101423

Flowering Poration-A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold

iScience. 2020 Aug 21;23(8):101423. doi: 10.1016/j.isci.2020.101423. Epub 2020 Jul 30.

Authors

Affiliations

¹ National Physical Laboratory, Hampton Road, Teddington TW11 0LW, UK; London Centre for Nanotechnology, University College London, London WC1H 0AH, UK; Department of Physics & Astronomy, University College London, London WC1E 6BT, UK.
² National Physical Laboratory, Hampton Road, Teddington TW11 0LW, UK.
³ Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester, UK.
⁴ School of Biomedical Sciences, University of Plymouth, Plymouth, Devon PL6 8BU, UK.
⁵ London Centre for Nanotechnology, University College London, London WC1H 0AH, UK; Department of Physics & Astronomy, University College London, London WC1E 6BT, UK.
⁶ National Physical Laboratory, Hampton Road, Teddington TW11 0LW, UK; Department of Physics, King's College London, Strand Lane, London WC2R, UK. Electronic address: max.ryadnov@npl.co.uk.

Abstract

Bacteriocins are a distinct family of antimicrobial proteins postulated to porate bacterial membranes. However, direct experimental evidence of pore formation by these proteins is lacking. Here we report a multi-mode poration mechanism induced by four-helix bacteriocins, epidermicin NI01 and aureocin A53. Using a combination of crystallography, spectroscopy, bioassays, and nanoscale imaging, we established that individual two-helix segments of epidermicin retain antibacterial activity but each of these segments adopts a particular poration mode. In the intact protein these segments act synergistically to balance out antibacterial and hemolytic activities. The study sets a precedent of multi-mode membrane disruption advancing the current understanding of structure-activity relationships in pore-forming proteins.

Keywords: Biological Sciences; Microbiology; Structural Biology.

Grants and funding

MR/R000328/1/MRC_/Medical Research Council/United Kingdom