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 language | English |
|---|---|
| Article number | e1006945 |
| Number of pages | 30 |
| Journal | PLoS Pathogens |
| Volume | 14 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 30 Mar 2018 |
Keywords
- Neisseria gonorrhoeae
- mitochondria
- outer membrane proteins
- apoptosis
- macrophages
- vesicles
- membrane proteins
- membrane staining
Cite this
}
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 journal › Article › Research › peer-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.
KW - Neisseria gonorrhoeae
KW - mitochondria
KW - outer membrane proteins
KW - apoptosis
KW - macrophages
KW - vesicles
KW - membrane proteins
KW - membrane staining
UR - http://www.scopus.com/inward/record.url?scp=85044830983&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1006945
DO - 10.1371/journal.ppat.1006945
M3 - Article
VL - 14
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 3
M1 - e1006945
ER -