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

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

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 an...

Full description

Bibliographic Details
Main Authors: Katharine Hammond, Helen Lewis, Samantha Halliwell, Florie Desriac, Brunello Nardone, Jascindra Ravi, Bart W. Hoogenboom, Mathew Upton, Jeremy P. Derrick, Maxim G. Ryadnov
Format: Article
Language:English
Published: Elsevier 2020-08-01
Series:iScience
Subjects:
Biological Sciences
Microbiology
Structural Biology
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004220306131
id doaj-e4ed096e2f10457d9312eb77c964e616
record_format Article
spelling doaj-e4ed096e2f10457d9312eb77c964e6162020-11-25T03:53:11ZengElsevieriScience2589-00422020-08-01238101423Flowering Poration—A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin FoldKatharine Hammond0Helen Lewis1Samantha Halliwell2Florie Desriac3Brunello Nardone4Jascindra Ravi5Bart W. Hoogenboom6Mathew Upton7Jeremy P. Derrick8Maxim G. Ryadnov9National 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, UKNational Physical Laboratory, Hampton Road, Teddington TW11 0LW, UKLydia 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, UKSchool of Biomedical Sciences, University of Plymouth, Plymouth, Devon PL6 8BU, UKNational Physical Laboratory, Hampton Road, Teddington TW11 0LW, UKNational Physical Laboratory, Hampton Road, Teddington TW11 0LW, UKLondon Centre for Nanotechnology, University College London, London WC1H 0AH, UK; Department of Physics & Astronomy, University College London, London WC1E 6BT, UKSchool of Biomedical Sciences, University of Plymouth, Plymouth, Devon PL6 8BU, UKLydia 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, UKNational Physical Laboratory, Hampton Road, Teddington TW11 0LW, UK; Department of Physics, King's College London, Strand Lane, London WC2R, UK; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004220306131Biological SciencesMicrobiologyStructural Biology
collection DOAJ
language English
format Article
sources DOAJ
author Katharine Hammond
Helen Lewis
Samantha Halliwell
Florie Desriac
Brunello Nardone
Jascindra Ravi
Bart W. Hoogenboom
Mathew Upton
Jeremy P. Derrick
Maxim G. Ryadnov
spellingShingle Katharine Hammond
Helen Lewis
Samantha Halliwell
Florie Desriac
Brunello Nardone
Jascindra Ravi
Bart W. Hoogenboom
Mathew Upton
Jeremy P. Derrick
Maxim G. Ryadnov
Flowering Poration—A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold
iScience
Biological Sciences
Microbiology
Structural Biology
author_facet Katharine Hammond
Helen Lewis
Samantha Halliwell
Florie Desriac
Brunello Nardone
Jascindra Ravi
Bart W. Hoogenboom
Mathew Upton
Jeremy P. Derrick
Maxim G. Ryadnov
author_sort Katharine Hammond
title Flowering Poration—A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold
title_short Flowering Poration—A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold
title_full Flowering Poration—A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold
title_fullStr Flowering Poration—A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold
title_full_unstemmed Flowering Poration—A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold
title_sort flowering poration—a synergistic multi-mode antibacterial mechanism by a bacteriocin fold
publisher Elsevier
series iScience
issn 2589-0042
publishDate 2020-08-01
description 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.
topic Biological Sciences
Microbiology
Structural Biology
url http://www.sciencedirect.com/science/article/pii/S2589004220306131
work_keys_str_mv AT katharinehammond floweringporationasynergisticmultimodeantibacterialmechanismbyabacteriocinfold
AT helenlewis floweringporationasynergisticmultimodeantibacterialmechanismbyabacteriocinfold
AT samanthahalliwell floweringporationasynergisticmultimodeantibacterialmechanismbyabacteriocinfold
AT floriedesriac floweringporationasynergisticmultimodeantibacterialmechanismbyabacteriocinfold
AT brunellonardone floweringporationasynergisticmultimodeantibacterialmechanismbyabacteriocinfold
AT jascindraravi floweringporationasynergisticmultimodeantibacterialmechanismbyabacteriocinfold
AT bartwhoogenboom floweringporationasynergisticmultimodeantibacterialmechanismbyabacteriocinfold
AT mathewupton floweringporationasynergisticmultimodeantibacterialmechanismbyabacteriocinfold
AT jeremypderrick floweringporationasynergisticmultimodeantibacterialmechanismbyabacteriocinfold
AT maximgryadnov floweringporationasynergisticmultimodeantibacterialmechanismbyabacteriocinfold
_version_ 1724479544848547840

Similar Items