Bacterial Toxins

Bacterial toxoids

Bacterial have evolved numerous mechanisms to subvert their hosts to enable increased infectivity and survival. Many of these mechanisms are mediated by multipart toxins, proteins which are secreted by the pathogen and subsequently endocytosed by host cells leading to many of the symptoms of the associated disease. These typically consist of separate protein subunits, one non-toxic subunit, responsible for cell binding, and one of more associated with membrane translocation and toxicity. The cell-binding/endocytosing subunit is frequently used a vaccine (e.g. Diphtheria/Pertussis).

In the case of the cholera toxin, the toxin has an AB5 architecture in which a pentameric non-toxic B-subunit surrounds an A2 helical segment which is, in turn, linked to the toxic A1 subunit via a disulfide bond. In collaboration with Professor Bruce Turnbull, we have made extensive use of the B subunit as a vehicle for cellular delivery, neuronal trafficking and as a model protein for protein engineering studies.

Publications in this area

Sortase-modified cholera toxoids show specific Golgi localization Darren C Machin, Daniel J Williamson, Peter Fisher, Victoria J Miller, Zoe LP Arnott, Charlotte ME Stevenson, Gemma C Wildsmith, James F Ross, Christopher W Wasson, Andrew Macdonald, Benjamin I Andrews, Daniel Ungar, W Bruce Turnbull, Michael E Webb Toxins (2024) 16, 194

The mutagenic plasticity of the Cholera toxin B-subunit surface residues; stability and affinity Cheuk Wang W. Au, Iain W. Manfield, Michael E. Webb, Emanuele Paci, W. Bruce Turnbull, James F. Ross Toxins (Basel) (2024) in press

Quantitative N- or C-Terminal Protein Labelling with Unactivated Peptides by Use of Sortases and a D-Aminopeptidase Zoe L.P. Arnott, Holly E. Morgan, Kristian Hollingsworth, Charlotte M. E. Stevenson, Lawrence J. Collins, Alexandra Tamasanu, Darren C. Machin, Jonathan P. Dolan, Tomasz P. Kaminski, Gemma C. Wildsmith, Daniel J. Williamson, Isabelle B. Pickles, Stuart L. Warriner, W. Bruce Turnbull and Michael E. Webb Angew. Chem. Int Ed. (2024) 63, e202310862

Membrane fusion mediated by non-covalent binding of re-engineered cholera toxin assemblies to glycolipids Sarah Wehrum, Lina Siukstaite, Daniel J Williamson, Thomas R Branson, Taras Sych, Josef Madl, Gemma C Wildsmith, Wenyue Dai, Erik Kempmann, James F Ross, Maren Thomsen, Michael E Webb, Winfried Römer, W Bruce Turnbull ACS Syn. Biol. (2022) 11, 3929-3938

Bio-orthogonal, bifunctional linker for engineering synthetic glycoproteins Ryan McBerney, Jonathan P Dolan, Emma E. Cawood, Michael E Webb, W Bruce Turnbull JACS Au (2022) 2, 2038–2047

Synthesis of cholera toxin B-subunit glycoconjugates using site-specific orthogonal oxime and sortase ligation reactions Jonathan P Dolan, Darren C Machin, Simone Dedola, Robert A Field, Michael E Webb, W Bruce Turnbull Frontiers in Chemistry (2022) 10 958272

In-depth characterization of a re-engineered cholera toxin manufacturing process using growth-decoupled production in Escherichia coli Natalia Danielewicz, Wenyue Dai, Francesca Rosato, Michael Webb, Gerald Striedner, Winfried Römer, W Bruce Turnbull, Juergen Mairhofer Toxins (Basel) (2022) 14 396

Piggybacking on the Cholera Toxin: Identification of a Toxoid-binding Protein as an Approach for Targeted Delivery of Proteins to Motor Neurons Matthew R Balmforth, Jessica Haigh, Vajinder Kumar, Wenyue Dai, Christian Tiede, Darren C Tomlinson, Jim Deuchars, Michael E Webb, W Bruce TurnbullBioconjug. Chem. (2021) 32 2205-2212

A versatile cholera toxin conjugate for neuronal targeting and tracing Jessica L Haigh, Daniel J Williamson, Emma Poole, Yuan Guo, Dejian Zhou, Michael E Webb, Susan A Deuchars, Jim Deuchars and W Bruce Turnbull Chem. Commun. (2020) 56, 6098-6501

A 'catch-and-release' receptor for the Cholera toxin Clare S. Mahon, Gemma C Wildsmith, Diksha Haksar, Eyleen de Poel, Roland Pieters, Jeffrey M Beekman, Michael E Webb and W Bruce Turnbull Faraday Disc. (2019) 219 112-127

Directed assembly of homo-pentameric cholera toxin B-subunit proteins into higher-order structures using coiled-coil appendages James F. Ross, Gemma C. Wildsmith, Michael Johnson, Daniel Hurdiss, Kristian Hollingsworth, Rebecca F. Thompson, Majid Mosayebi, Chi H. Trinh, Emanuele Paci, Arwen R. Pearson, Michael E. Webb and W. Bruce Turnbull J. Amer. Chem. Soc. (2019) 141, 5211-5219