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

Pankaj Deo, Seong H. Chow, Iain D. Hay, Oded Kleifeld, Adam Costin, Kirstin D. Elgass, Jhih-Hang Jiang, Georg Ramm, Kipros Gabriel, Gordon Dougan, Trevor Lithgow, Eva Heinz, Thomas Naderer

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

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.

Original languageEnglish
Article numbere1006945
Number of pages30
JournalPLoS Pathogens
Volume14
Issue number3
DOIs
Publication statusPublished - 30 Mar 2018

Keywords

  • Neisseria gonorrhoeae
  • mitochondria
  • outer membrane proteins
  • apoptosis
  • macrophages
  • vesicles
  • membrane proteins
  • membrane staining

Cite this

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title = "Outer membrane vesicles from Neisseria gonorrhoeae target PorB to mitochondria and induce apoptosis",
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.",
keywords = "Neisseria gonorrhoeae, mitochondria, outer membrane proteins, apoptosis, macrophages, vesicles, membrane proteins, membrane staining",
author = "Pankaj Deo and Chow, {Seong H.} and Hay, {Iain D.} and Oded Kleifeld and Adam Costin and Elgass, {Kirstin D.} and Jhih-Hang Jiang and Georg Ramm and Kipros Gabriel and Gordon Dougan and Trevor Lithgow and Eva Heinz and Thomas Naderer",
year = "2018",
month = "3",
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doi = "10.1371/journal.ppat.1006945",
language = "English",
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Outer membrane vesicles from Neisseria gonorrhoeae target PorB to mitochondria and induce apoptosis. / Deo, Pankaj; Chow, Seong H.; Hay, Iain D.; Kleifeld, Oded; Costin, Adam; Elgass, Kirstin D.; Jiang, Jhih-Hang; Ramm, Georg; Gabriel, Kipros; Dougan, Gordon; Lithgow, Trevor; Heinz, Eva; Naderer, Thomas.

In: PLoS Pathogens, Vol. 14, No. 3, e1006945, 30.03.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Outer membrane vesicles from Neisseria gonorrhoeae target PorB to mitochondria and induce apoptosis

AU - Deo, Pankaj

AU - Chow, Seong H.

AU - Hay, Iain D.

AU - Kleifeld, Oded

AU - Costin, Adam

AU - Elgass, Kirstin D.

AU - Jiang, Jhih-Hang

AU - Ramm, Georg

AU - Gabriel, Kipros

AU - Dougan, Gordon

AU - Lithgow, Trevor

AU - Heinz, Eva

AU - Naderer, Thomas

PY - 2018/3/30

Y1 - 2018/3/30

N2 - 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.

AB - 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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KW - outer membrane proteins

KW - apoptosis

KW - macrophages

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KW - membrane proteins

KW - membrane staining

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SN - 1553-7366

IS - 3

M1 - e1006945

ER -