title: Haemolysis induced by α-toxin from Staphylococcus aureus requires P2X receptor activation.
abstract: Recently, it was documented that α-haemolysin (HlyA) from Escherichia coli uses erythrocyte P2 receptors cause lysis. This finding was surprising as it appeared firmly established that HlyA-dependent pore formation per se is sufficient for full cell lysis. We discovered that HlyA induced a sequential process of shrinkage and swelling and that the final haemolysis is completely prevented by blockers of P2X receptors and pannexin channels. This finding has potential clinical relevance as it may offer specific pharmacological interference to ameliorate haemolysis inflicted by pore-forming bacterial toxins. In this context, it is essential to know whether this is specific to HlyA-induced cell damage or if other bacterial pore-forming toxins involve purinergic signals to orchestrate haemolysis. Here, we investigate if the haemolysis produced by α-toxin from Staphylococcus aureus involves P2 receptor activation. We observed that α-toxin-induced haemolysis is completely blocked by the unselective P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid. Moreover, several selective blockers of P2X(1) and P2X(7) ionotropic receptors abolished haemolysis in murine and equine erythrocytes. Inhibitors of pannexin channels partially reduced the α-toxin induced lysis. Thus, we conclude that α-toxin, similar to HlyA from E. coli produces cell damage by specific activation of a purinergic signalling cascade. These data indicate that pore-forming toxins in general require purinergic signalling to elicit their toxicity.
authors.affiliation: Department of Biomedicine, Aarhus University, Ole Worms Allé 4, build. 1160, 8000, Aarhus C, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Skals
authors.forename: Jens
authors.initials: J
authors.lastname: Leipziger
authors.forename: Helle A
authors.initials: HA
authors.lastname: Praetorius
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D002229:Carbenoxolone / Q000494:pharmacology; D017630:Connexins / Q000037:antagonists & inhibitors; D029968:Escherichia coli Proteins / Q000633:toxicity; D005260:Female; D006460:Hemolysin Proteins / Q000633:toxicity*; D006461:Hemolysis / Q000187:drug effects*; D006736:Horses; D006801:Humans; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D058469:Receptors, Purinergic P2X / Q000187:drug effects / Q000502:physiology*; D058486:Receptors, Purinergic P2X7 / Q000502:physiology
chemical_list: D001427:Bacterial Toxins; D017630:Connexins; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; C036507:Hlya protein, E coli; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D058469:Receptors, Purinergic P2X; D058486:Receptors, Purinergic P2X7; C021091:staphylococcal alpha-toxin; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D002229:Carbenoxolone