Your browser doesn't support javascript.
loading
Auto-Assembling Detoxified Staphylococcus aureus Alpha-Hemolysin Mimicking the Wild-Type Cytolytic Toxin.
Fiaschi, Luigi; Di Palo, Benedetta; Scarselli, Maria; Pozzi, Clarissa; Tomaszewski, Kelly; Galletti, Bruno; Nardi-Dei, Vincenzo; Arcidiacono, Letizia; Mishra, Ravi P N; Mori, Elena; Pallaoro, Michele; Falugi, Fabiana; Torre, Antonina; Fontana, Maria Rita; Soriani, Marco; Bubeck Wardenburg, Juliane; Grandi, Guido; Rappuoli, Rino; Ferlenghi, Ilaria; Bagnoli, Fabio.
Afiliação
  • Fiaschi L; Novartis Vaccines and Diagnostics, now GSK Vaccines, Siena, Italy.
  • Di Palo B; GSK Vaccines, Research Center, Siena, Italy.
  • Scarselli M; GSK Vaccines, Research Center, Siena, Italy.
  • Pozzi C; GSK Vaccines, Research Center, Siena, Italy.
  • Tomaszewski K; Departments of Pediatrics and Microbiology, University of Chicago, Chicago, Illinois, USA.
  • Galletti B; GSK Vaccines, Research Center, Siena, Italy.
  • Nardi-Dei V; GSK Vaccines, Research Center, Siena, Italy.
  • Arcidiacono L; GSK Vaccines, Research Center, Siena, Italy.
  • Mishra RP; Novartis Vaccines and Diagnostics, now GSK Vaccines, Siena, Italy.
  • Mori E; GSK Vaccines, Research Center, Siena, Italy.
  • Pallaoro M; GSK Vaccines, Research Center, Siena, Italy.
  • Falugi F; Novartis Vaccines and Diagnostics, now GSK Vaccines, Siena, Italy.
  • Torre A; Novartis Vaccines and Diagnostics, now GSK Vaccines, Siena, Italy.
  • Fontana MR; Novartis Vaccines and Diagnostics, now GSK Vaccines, Siena, Italy.
  • Soriani M; GSK Vaccines, Research Center, Siena, Italy.
  • Bubeck Wardenburg J; Departments of Pediatrics and Microbiology, University of Chicago, Chicago, Illinois, USA.
  • Grandi G; Novartis Vaccines and Diagnostics, now GSK Vaccines, Siena, Italy.
  • Rappuoli R; GSK Vaccines, Research Center, Siena, Italy.
  • Ferlenghi I; GSK Vaccines, Research Center, Siena, Italy ilaria.x.ferlenghi@gsk.com fabio.x.bagnoli@gsk.com.
  • Bagnoli F; GSK Vaccines, Research Center, Siena, Italy ilaria.x.ferlenghi@gsk.com fabio.x.bagnoli@gsk.com.
Clin Vaccine Immunol ; 23(6): 442-50, 2016 06.
Article em En | MEDLINE | ID: mdl-27030589
Staphylococcus aureus alpha-hemolysin (Hla) assembles into heptameric pores on the host cell membrane, causing lysis, apoptosis, and junction disruption. Herein, we present the design of a newly engineered S. aureus alpha-toxin, HlaPSGS, which lacks the predicted membrane-spanning stem domain. This protein is able to form heptamers in aqueous solution in the absence of lipophilic substrata, and its structure, obtained by transmission electron microscopy and single-particle reconstruction analysis, resembles the cap of the wild-type cytolytic Hla pore. HlaPSGS was found to be impaired in binding to host cells and to its receptor ADAM10 and to lack hemolytic and cytotoxic activity. Immunological studies using human sera as well as sera from mice convalescent from S. aureus infection suggested that the heptameric conformation of HlaPSGS mimics epitopes exposed by the cytolytic Hla pore during infection. Finally, immunization with this newly engineered Hla generated high protective immunity against staphylococcal infection in mice. Overall, this study provides unprecedented data on the natural immune response against Hla and suggests that the heptameric HlaPSGS is a highly valuable vaccine candidate against S. aureus.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções Estafilocócicas / Staphylococcus aureus / Toxinas Bacterianas / Mimetismo Molecular / Proteínas Hemolisinas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções Estafilocócicas / Staphylococcus aureus / Toxinas Bacterianas / Mimetismo Molecular / Proteínas Hemolisinas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article