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Lookup NU author(s): Dr Adam WollmanORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Staphylococcus aureus Panton-Valentine leukocidin is a pore-forming toxin targeting the human C5a receptor (hC5aR), enabling this pathogen to battle the immune response by destroying phagocytes through targeted lysis. The mechanisms that contribute to rapid cell lysis are largely unexplored. Here, we show that cell lysis may be enabled by a process of toxins targeting receptor clusters and present indirect evidence for receptor "recycling" that allows multiple toxin pores to be formed close together. With the use of live cell single-molecule super-resolution imaging, Förster resonance energy transfer and nanoscale total internal reflection fluorescence colocalization microscopy, we visualized toxin pore formation in the presence of its natural docking ligand. We demonstrate disassociation of hC5aR from toxin complexes and simultaneous binding of new ligands. This effect may free mobile receptors to amplify hyperinflammatory reactions in early stages of microbial infections and have implications for several other similar bicomponent toxins and the design of new antibiotics.-Haapasalo, K., Wollman, A. J. M., de Haas, C. J. C., van Kessel, K. P. M., van Strijp, J. A. G., Leake, M. C. Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration.
Author(s): Haapasalo K, Wollman AJM, de Haas CJC, van Kessel KPM, van Strijp JAG, Leake MC
Publication type: Article
Publication status: Published
Journal: The FASEB Journal
Year: 2019
Volume: 33
Issue: 3
Pages: 3807-3824
Print publication date: 01/03/2019
Online publication date: 03/12/2018
Acceptance date: 29/10/2018
Date deposited: 10/02/2020
ISSN (print): 0892-6638
ISSN (electronic): 1530-6860
Publisher: Federation of American Societies for Experimental Biology
URL: https://doi.org/10.1096/fj.201801910R
DOI: 10.1096/fj.201801910R
PubMed id: 30509126
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