Scientists at Monash University say they discovered how the gonorrhea superbug evades the immune system, opening up a way for therapies that prevent this process and allowing the body's natural defenses to kill the bug. The team published its study (“Outer Membrane Vesicles from Neisseria gonorrhoeae Target PorB to Mitochondria and Induce Apoptosis”) in PLOS Pathogens.
Thomas Naderer, Ph.D., and Pankaj Deo, Ph.D., and their team from the Monash Biomedicine Discovery Institute describe how Neisseria gonorrhoea creates vesicles that attack immune cells.
“Neisseria gonorrhorae 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. gonorrhorae to mitochondria and whether it modulates innate immune cells, such as macrophages, remains unclear. Here, we show that N. gonorrhorae secretes PorB via outer membrane vesicles (OMVs). Purified OMVs contained primarily outer membrane proteins including oligomeric PorB,” write the investigators.
“The porin was targeted to mitochondria of macrophages after exposure to purified OMVs and wild type N. gonorrhorae. 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. gonorrhorae utilizes OMVs to target PorB to mitochondria and to induce apoptosis in macrophages, thus affecting innate immunity.”
Using super-resolution microscopy, the team found that these membrane vesicles interacted with macrophages, triggering these to die in an orchestrated suicide process. Dr. Naderer said that this new understanding of how the gonorrhea bacteria interact and cause the death of immune system cells “may lead to strategies to combat gonorrhea infection and its symptoms”.
The research may also provide information as to how other bacteria evade the immune system and be unaffected by antibiotics, he added.
