title: Release of the type I secreted alpha-haemolysin via outer membrane vesicles from Escherichia coli.
abstract: The alpha-haemolysin is an important virulence factor commonly expressed by extraintestinal pathogenic Escherichia coli. The secretion of the alpha-haemolysin is mediated by the type I secretion system and the toxin reaches the extracellular space without the formation of periplasmic intermediates presumably in a soluble form. Surprisingly, we found that a fraction of this type I secreted protein is located within outer membrane vesicles (OMVs) that are released by the bacteria. The alpha-haemolysin appeared very tightly associated with the OMVs as judged by dissociation assays and proteinase susceptibility tests. The alpha-haemolysin in OMVs was cytotoxically active and caused lysis of red blood cells. The OMVs containing the alpha-haemolysin were distinct from the OMVs not containing alpha-haemolysin, showing a lower density. Furthermore, they differed in protein composition and one component of the type I secretion system, the TolC protein, was found in the lower density vesicles. Studies of natural isolates of E. coli demonstrated that the localization of alpha-haemolysin in OMVs is a common feature among haemolytic strains. We propose an alternative pathway for the transport of the type I secreted alpha-haemolysin from the bacteria to the host cells during bacterial infections.
authors.affiliation: Department of Molecular Biology, Umeå University, S-90187 Umeå, Sweden. cbalsalobre@ub.edu
authors.forename: Carlos
authors.initials: C
authors.lastname: Balsalobre
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Silván
authors.forename: Stina
authors.initials: S
authors.lastname: Berglund
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Mizunoe
authors.forename: Bernt Eric
authors.initials: BE
authors.lastname: Uhlin
authors.forename: Sun Nyunt
authors.initials: SN
authors.lastname: Wai
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D022162:Cytoplasmic Vesicles / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D004926:Escherichia coli / Q000166:cytology / Q000378:metabolism* / Q000472:pathogenicity; D004927:Escherichia coli Infections; D029968:Escherichia coli Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006367:HeLa Cells; D006460:Hemolysin Proteins / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins
chemical_list: D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D005227:Fatty Acids; D006460:Hemolysin Proteins; D026901:Membrane Transport Proteins; C073126:tolC protein, E coli