Induction of eryptosis by low concentrations of E. coli alpha-hemolysin

FERNANDA CARRIZO; SABINA MATÉ; LAURA BAKÁS; VANESA HERLAX

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015 vol. 1848 p. 2779 - 2788

0005-2736

Uropathogenic strains of Escherichia coli deliver the toxin alpha-hemolysin (HlyA) to optimize the host environmentfor the spread of infection. It was reported that at high concentrations, the toxin forms pores in eukaryoticmembranes, leading to cell lysis,while lower concentrations have appeared to interfere with host?cell-signalingpathways causing cell death by apoptosis. Nevertheless, what is not clear is how often HlyA reaches levels thatare high enough to lyse host target cells during the course of an infection. In the present investigation, we demonstratethat a lowtoxin concentration induces the suicidal death of erythrocytes (eryptosis), the major cell typepresent in blood. Eryptosis is triggered both by an increment in intracellular calcium and by ceramide. Since wehave previously demonstrated that a low concentration of HlyA induces an increase in intraerythrocyte calcium,in the present experiments we have shown that this ion activates calpains, which hydrolyze skeleton proteinssuch as spectrin, ankyrin, protein 4.1 and the electrophoretic Band-3 species, thus resulting in morphologicchanges in the erythrocytes. We furthermore observed that a low toxin concentration induced the activationof endogenous sphingomyelinases that in turn increased the amount of ceramide in erythrocyte membranes.Both spectrin proteolysis and ceramide formation may cause the exposure of phosphatidylserine on the membraneso as to trigger a macrophage engulfment of the erythrocyte. By this means eryptosis may be an advantageousmechanism for removing defective erythrocytes before hemolysis.