A novel mechanism for the biogenesis of outer membrane vesicles in Gram-negative bacteria

Sandro Roier, Franz G. Zingl, Fatih Cakar, Sanel Durakovic, Paul Kohl, Thomas O. Eichmann, Lisa Klug, Bernhard Gadermaier, Katharina Weinzerl, Ruth Prassl, Achim Lass, Günther Daum, Joachim Reidl, Mario F. Feldman and Stefan Schild ()
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Sandro Roier: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz
Franz G. Zingl: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz
Fatih Cakar: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz
Sanel Durakovic: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz
Paul Kohl: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz
Thomas O. Eichmann: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz
Lisa Klug: Institute of Biochemistry, Graz University of Technology, NAWI Graz, BioTechMed-Graz
Bernhard Gadermaier: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz
Katharina Weinzerl: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz
Ruth Prassl: Institute of Biophysics, Medical University of Graz, BioTechMed-Graz
Achim Lass: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz
Günther Daum: Institute of Biochemistry, Graz University of Technology, NAWI Graz, BioTechMed-Graz
Joachim Reidl: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz
Mario F. Feldman: University of Alberta
Stefan Schild: Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10515

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