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    Outer membrane vesicles from Neisseria gonorrhoeae target PorB to mitochondria and induce apoptosis

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    Author
    Deo, P; Chow, SH; Hay, ID; Kleifeld, O; Costin, A; Elgass, KD; Jiang, J-H; Ramm, G; Gabriel, K; Dougan, G; ...
    Date
    2018-03-01
    Source Title
    PLoS Pathogens
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Dougan, Gordon; Jiang, Jhih-Hang
    Affiliation
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Deo, P., Chow, S. H., Hay, I. D., Kleifeld, O., Costin, A., Elgass, K. D., Jiang, J. -H., Ramm, G., Gabriel, K., Dougan, G., Lithgow, T., Heinz, E. & Naderer, T. (2018). Outer membrane vesicles from Neisseria gonorrhoeae target PorB to mitochondria and induce apoptosis. PLOS PATHOGENS, 14 (3), https://doi.org/10.1371/journal.ppat.1006945.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/254740
    DOI
    10.1371/journal.ppat.1006945
    Abstract
    Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhoea by evading innate immunity. Colonizing the mucosa of the reproductive tract depends on the bacterial outer membrane porin, PorB, which is essential for ion and nutrient uptake. PorB is also targeted to host mitochondria and regulates apoptosis pathways to promote infections. How PorB traffics from the outer membrane of N. gonorrhoeae to mitochondria and whether it modulates innate immune cells, such as macrophages, remains unclear. Here, we show that N. gonorrhoeae secretes PorB via outer membrane vesicles (OMVs). Purified OMVs contained primarily outer membrane proteins including oligomeric PorB. The porin was targeted to mitochondria of macrophages after exposure to purified OMVs and wild type N. gonorrhoeae. This was associated with loss of mitochondrial membrane potential, release of cytochrome c, activation of apoptotic caspases and cell death in a time-dependent manner. Consistent with this, OMV-induced macrophage death was prevented with the pan-caspase inhibitor, Q-VD-PH. This shows that N. gonorrhoeae utilizes OMVs to target PorB to mitochondria and to induce apoptosis in macrophages, thus affecting innate immunity.

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