Gutenberg Open Science: P2X-receptor antagonists inhibit the interaction of S. aureus hemolysin A with membranes

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8055

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DC Field	Value	Language
dc.contributor.author	Schwiering, Markus	-
dc.contributor.author	Husmann, Matthias	-
dc.contributor.author	Hellmann, Nadja	-
dc.date.accessioned	2022-10-17T07:34:26Z	-
dc.date.available	2022-10-17T07:34:26Z	-
dc.date.issued	2017
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/8070	-
dc.description.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.	en_GB
dc.description.sponsorship	DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	P2X-receptor antagonists inhibit the interaction of S. aureus hemolysin A with membranes	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-8055	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.department	FB 09 Chemie, Pharmazie u. Geowissensch.	de
jgu.organisation.number	2700	-
jgu.organisation.number	7950	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Toxins	de
jgu.journal.volume	9	de
jgu.journal.issue	10	de
jgu.pages.alternative	Art. 332	de
jgu.publisher.year	2017	-
jgu.publisher.name	MDPI	de
jgu.publisher.place	Basel	de
jgu.publisher.uri	http://dx.doi.org/10.3390/toxins9100332	de
jgu.publisher.issn	2072-6651	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
opus.date.modified	2018-01-24T09:00:42Z
opus.subject.dfgcode	00-000
opus.organisation.string	FB 09: Chemie, Pharmazie und Geowissenschaften: Institut für Pharmazie	de_DE
opus.organisation.string	FB 04: Medizin: Institut für Medizinische Mikrobiologie und Hygiene	de_DE
opus.identifier.opusid	57524
opus.institute.number	0908
opus.institute.number	0408
opus.metadataonly	false
opus.type.contenttype	Keine	de_DE
opus.type.contenttype	None	en_EN
opus.affiliated	Husmann, Matthias
opus.affiliated	Hellmann, Nadja
jgu.publisher.doi	10.3390/toxins9100332	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)

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