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
Affiliations
Katharine Hammond
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
Helen Lewis
National Physical Laboratory, Hampton Road, Teddington TW11 0LW, UK
Samantha Halliwell
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
Florie Desriac
School of Biomedical Sciences, University of Plymouth, Plymouth, Devon PL6 8BU, UK
Brunello Nardone
National Physical Laboratory, Hampton Road, Teddington TW11 0LW, UK
Jascindra Ravi
National Physical Laboratory, Hampton Road, Teddington TW11 0LW, UK
Bart W. Hoogenboom
London Centre for Nanotechnology, University College London, London WC1H 0AH, UK; Department of Physics & Astronomy, University College London, London WC1E 6BT, UK
Mathew Upton
School of Biomedical Sciences, University of Plymouth, Plymouth, Devon PL6 8BU, UK
Jeremy P. Derrick
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
Maxim G. Ryadnov
National Physical Laboratory, Hampton Road, Teddington TW11 0LW, UK; Department of Physics, King's College London, Strand Lane, London WC2R, UK; Corresponding author
Summary: 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.
