Autoren:	Schwiering, Markus Husmann, Matthias Hellmann, Nadja
Titel:	P2X-receptor antagonists inhibit the interaction of S. aureus hemolysin A with membranes
Online-Publikationsdatum:	17-Okt-2022
Erscheinungsdatum:	2017
Sprache des Dokuments:	Englisch
Zusammenfassung/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-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin FB 09 Chemie, Pharmazie u. Geowissensch.
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8055
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Toxins 9 10
Seitenzahl oder Artikelnummer:	Art. 332
Verlag:	MDPI
Verlagsort:	Basel
Erscheinungsdatum:	2017
ISSN:	2072-6651
URL der Originalveröffentlichung:	http://dx.doi.org/10.3390/toxins9100332
DOI der Originalveröffentlichung:	10.3390/toxins9100332
Enthalten in den Sammlungen:	DFG-OA-Publizieren (2012 - 2017)