Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-8055
Authors: | Schwiering, Markus Husmann, Matthias Hellmann, Nadja |
Title: | P2X-receptor antagonists inhibit the interaction of S. aureus hemolysin A with membranes |
Online publication date: | 17-Oct-2022 |
Year of first publication: | 2017 |
Language: | english |
Abstract: | The pore forming hemolysin A, Hla, is a major virulence factor of Staphylococcus aureus. apparently, 1–2 pore(s) per cell suffice(s) to cause cell death. accumulated experimental evidence points towards a major role of atp-gated purinergic receptors (p2xr) for hemolysis caused by hla, complement and other pore forming proteins, presumably by increasing membrane permeability. indeed, in experiments employing rabbit erythrocytes, inhibitory concentrations of frequently employed p2xr-antagonists were in a similar range as previously reported for erythrocytes of other species and other toxins. however, hla-dependent hemolysis was not enhanced by extracellular atp, and oxidized adenosinetriphosphate (oxatp) had only a minor inhibitory effect. unexpectedly, p2xr-inhibitors also prevented hla-induced lysis of pure lipid membranes, demonstrating that the inhibition did not even depend on the presence of p2xr. fluorescence microscopy and gel-electrophoresis clearly revealed that p2xr-inhibitors interfere with binding and subsequent oligomerisation of hla with membranes. similar results were obtained employing hacat-cells. furthermore, calorimetric data and hemolysis experiments with hla pre-treated with pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (ppads) showed that this compound directly binds to hla. our results call for a critical re-assessment of the appealing concept, which suggests that p2xr are general amplifiers of damage by pore-forming proteins. |
DDC: | 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin FB 09 Chemie, Pharmazie u. Geowissensch. |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-8055 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Toxins 9 10 |
Pages or article number: | Art. 332 |
Publisher: | MDPI |
Publisher place: | Basel |
Issue date: | 2017 |
ISSN: | 2072-6651 |
Publisher URL: | http://dx.doi.org/10.3390/toxins9100332 |
Publisher DOI: | 10.3390/toxins9100332 |
Appears in collections: | DFG-OA-Publizieren (2012 - 2017) |
Files in This Item:
File | Description | Size | Format | ||
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![]() | p2xreceptor_antagonists_inhib-20220925164739133.pdf | 7.4 MB | Adobe PDF | View/Open |