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Nat Commun. 2016 Jan 25;7:10515. doi: 10.1038/ncomms10515.

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

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Institute of Molecular Biosciences, University of Graz, NAWI Graz, BioTechMed-Graz, Humboldtstraße 50, A-8010 Graz, Austria.
Institute of Biochemistry, Graz University of Technology, NAWI Graz, BioTechMed-Graz, Petersgasse 12/2, A-8010 Graz, Austria.
Institute of Biophysics, Medical University of Graz, BioTechMed-Graz, Harrachgasse 21, A-8010 Graz, Austria.
Department of Biological Sciences, University of Alberta, CW405 Biological Sciences Building, Edmonton, Alberta, Canada T6G 2E9.


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.

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