Novel evidence for the specific interaction between cholesterol and α-haemolysin of Escherichia coli

Several toxins that interact with animal cells present some kind of interaction with cholesterol (Cho) or sphingomyelin. In the present work we demonstrate that alpha hemolysin of E. coli (HlyA) interacts directly with Chocholesterol, resulting in one of the first reported toxins secreted by Gram ne...

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Detalles Bibliográficos
Autores: Vazquez, Romina Florencia, Maté, Sabina María, Bakás, Laura S., Fernández, Marisa Mariel, Malchiodi, Emilio Luis, Herlax, Vanesa Silvana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/8041
Acceso en línea:http://hdl.handle.net/11336/8041
Access Level:acceso abierto
Palabra clave:Cholesterol
Rtx Toxin
Spr
Biacore
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
Descripción
Sumario:Several toxins that interact with animal cells present some kind of interaction with cholesterol (Cho) or sphingomyelin. In the present work we demonstrate that alpha hemolysin of E. coli (HlyA) interacts directly with Chocholesterol, resulting in one of the first reported toxins secreted by Gram negative bacteria and the first reported member of the RTX toxin family that participates in the interaction with this sterol. We have recently reported that HlyA became associated with detergent-resistant membranes enriched in sphingomyelin and Chocholesterol; moreover, after Cho depletion, toxin oligomerization and hence hemolytic activity diminishes. Considering these results we studied the insertion process by monolayer technique, finding that HlyA insertion into membranes is favouredfavored in sphingomyelin and Chocholesterol-containing membranes. Taking into account this result, the direct interaction with either of the lipids was studied by lipid dot blot, lysis inhibition and surface plasmon resonance assays. Results demonstrated that there isit exists a direct interaction between Chocholesterol and HlyA that seems to favoursfavors a conformational state of the protein that allows the correct insertion into the membrane and further oligomerization to pore formation.