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Haemolysis induced by α-toxin from Staphylococcus aureus requires P2X receptor activation

  • Ion Channels, Receptors and Transporters
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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 P2X1 and P2X7 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.

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Acknowledgements

We thank Edith Bjoern Moeller for the skilled technical assistance and Niklas R. Jorgensen for the collaboration with regards the P2X7−/− mice. The project is financially supported by the Danish Medical Research Council, Danish National Research Foundation and the Aarhus University Research Foundation.

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  1. Department of Biomedicine, Aarhus University, Ole Worms Allé 4, build. 1160, 8000, Aarhus C, Denmark

    Marianne Skals, Jens Leipziger & Helle A. Praetorius

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  1. Marianne Skals
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  2. Jens Leipziger
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Correspondence to Helle A. Praetorius.

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Skals, M., Leipziger, J. & Praetorius, H.A. Haemolysis induced by α-toxin from Staphylococcus aureus requires P2X receptor activation. Pflugers Arch - Eur J Physiol 462, 669–679 (2011). https://doi.org/10.1007/s00424-011-1010-x

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