title: A novel mechanism for the biogenesis of outer membrane vesicles in Gram-negative bacteria.
abstract: Bacterial outer membrane vesicles (OMVs) have important biological roles in pathogenesis and intercellular interactions, but a general mechanism of OMV formation is lacking. Here we show that the VacJ/Yrb ABC (ATP-binding cassette) transport system, a proposed phospholipid transporter, is involved in OMV formation. Deletion or repression of VacJ/Yrb increases OMV production in two distantly related Gram-negative bacteria, Haemophilus influenzae and Vibrio cholerae. Lipidome analyses demonstrate that OMVs from VacJ/Yrb-defective mutants in H. influenzae are enriched in phospholipids and certain fatty acids. Furthermore, we demonstrate that OMV production and regulation of the VacJ/Yrb ABC transport system respond to iron starvation. Our results suggest a new general mechanism of OMV biogenesis based on phospholipid accumulation in the outer leaflet of the outer membrane. This mechanism is highly conserved among Gram-negative bacteria, provides a means for regulation, can account for OMV formation under all growth conditions, and might have important pathophysiological roles in vivo.
authors.affiliation: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
authors.forename: Sandro
authors.initials: S
authors.lastname: Roier
authors.affiliation: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
authors.forename: Franz G
authors.initials: FG
authors.lastname: Zingl
authors.affiliation: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
authors.forename: Fatih
authors.initials: F
authors.lastname: Cakar
authors.affiliation: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
authors.forename: Sanel
authors.initials: S
authors.lastname: Durakovic
authors.affiliation: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Kohl
authors.affiliation: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Eichmann
authors.affiliation: Institute of Biochemistry, Graz University of Technology, NAWI Graz, BioTechMed-Graz, Petersgasse 12/2, A-8010 Graz, Austria.
authors.forename: Lisa
authors.initials: L
authors.lastname: Klug
authors.affiliation: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gadermaier
authors.affiliation: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Weinzerl
authors.affiliation: Institute of Biophysics, Medical University of Graz, BioTechMed-Graz, Harrachgasse 21, A-8010 Graz, Austria.
authors.forename: Ruth
authors.initials: R
authors.lastname: Prassl
authors.affiliation: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
authors.forename: Achim
authors.initials: A
authors.lastname: Lass
authors.affiliation: Institute of Biochemistry, Graz University of Technology, NAWI Graz, BioTechMed-Graz, Petersgasse 12/2, A-8010 Graz, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Daum
authors.affiliation: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
authors.forename: Joachim
authors.initials: J
authors.lastname: Reidl
authors.affiliation: Department of Biological Sciences, University of Alberta, CW405 Biological Sciences Building, Edmonton, Alberta, Canada T6G 2E9.
authors.forename: Mario F
authors.initials: MF
authors.lastname: Feldman
authors.affiliation: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schild
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D022162:Cytoplasmic Vesicles / Q000502:physiology*; D004926:Escherichia coli; D005260:Female; D006193:Haemophilus influenzae / Q000502:physiology*; D008807:Mice, Inbred BALB C; D001678:Organelle Biogenesis; D014734:Vibrio cholerae / Q000502:physiology*
chemical_list: D018528:ATP-Binding Cassette Transporters