Escherichia coli is the dominant facultative bacterium in the normal intestinal flora. E.coli is, however, also responsible for the majority of serious extra intestinal infections. There are distinct serotypical differences between facultative and invasive E.coli-strains. Invasive strains frequently produce virulence factors as a-hemolysin (HlyA), which causes hemolysis by forming pores in the erythrocyte membrane. The present study reveals that this pore-formation per se is not sufficient to produce hemolysis. HlyA demands intact purinergic signaling to mediate its hemolytic action.

Non-selective ATP-receptor (P2) antagonists (PPADS, suramin) and ATP scavengers (apyrase, hexokinase) concentration dependently inhibited HlyA-induced lysis of equine, murine and human erythrocytes. The pattern of responsiveness to more selective P2-antagonists indicates that the involved P2 receptor is a combination of P2X₁ and P2X₇ in all three species. In addition, our results also implicate that the pore-protein, pannexin1, is necessary for HlyA-induced hemolysis, as non-selective inhibitors of this channel significantly reduced hemolysis in the three species. In conclusion, activation of P2X receptors is a requirement for hemolysis induced by the bacterial toxin, HlyA. These findings potentially have clinical perspectives as P2-antagonists may ameliorate symptoms during sepsis with hemolytic bacteria.