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

PLoS Pathog. 2018 Mar 30;14(3):e1006945. doi: 10.1371/journal.ppat.1006945. eCollection 2018 Mar.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Membrane / metabolism*
  • Gonorrhea / microbiology
  • Gonorrhea / pathology*
  • Humans
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Macrophages / pathology*
  • Membrane Potential, Mitochondrial
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • Mitochondria / microbiology
  • Mitochondria / pathology*
  • Neisseria gonorrhoeae / pathogenicity*
  • Porins / genetics
  • Porins / metabolism*

Substances

  • Porins
  • porin protein, Neisseria

Grant support

The study was supported by the National Health and Medical Research Council, Canberra, Australia (www.nhmrc.gov.au) with a project grant (1024839, TN) and program grant (606788, GD and TJL). TN is an Australian Research Council Future Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.