MALCHIODI Emilio Luis
Novel evidence for the specific interaction between cholesterol and alpha hemolysin of Escherichia coli
ROMINA F. VAZQUEZ; SABINA M. MATÉ; LAURA S. BAKÁS; MARISA M. FERNÁNDEZ; EMILIO L. MALCHIODI; VANESA S. HERLAX
PORTLAND PRESS LTD
Lugar: Londres; Año: 2014 vol. 458 p. 481 - 489
Several toxins that act on animal cells present different but specific interactions with cholesterol or sphingomyelin. In the present investigation we demonstrate that alpha-hemolysin of Escherichia coli (HlyA) interacts directly with cholesterol. We have recently reported that HlyA became associated with detergent-resistant membranes enriched in cholesterol and sphingomyelin; moreover, toxin oligomerization?and hence hemolytic activity?diminishes in cholesterol depleted erythrocytes. Considering these results, we studied the insertion process -essential step in the lytic mechanism- by the monolayer technique, finding that HlyA insertion is favored in cholesterol - and sphingomyelin -containing membranes. On the basis of this result, we studied the direct interaction with either of the lipids by lipid dot blotting, lysis inhibition, and surface-plasmon? resonance assays. The results demonstrated that an interaction between cholesterol and HlyA exists that seems to favor a conformational state of the protein allowing the correct insertion into the membrane and further oligomerization to form pores.