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

Area of Science:

• Microbiology
• Immunology
• Cell Biology

Background:

• Neisseria gonorrhoeae causes gonorrhoea, evading innate immunity.
• The outer membrane porin PorB is crucial for N. gonorrhoeae colonization and targets host mitochondria.
• Mechanisms of PorB trafficking and its effect on innate immune cells like macrophages are unknown.

Purpose of the Study:

• To investigate how Neisseria gonorrhoeae PorB reaches host mitochondria.
• To determine if PorB affects innate immune cells, specifically macrophages.
• To elucidate the role of outer membrane vesicles in this process.

Main Methods:

• N. gonorrhoeae outer membrane vesicles (OMVs) were isolated and characterized.
• Macrophage cultures were exposed to purified OMVs and wild-type N. gonorrhoeae.
• Mitochondrial function, apoptosis markers (cytochrome c, caspases), and cell death were assessed.
• The effect of a pan-caspase inhibitor was evaluated.

Main Results:

• N. gonorrhoeae secretes PorB via OMVs, with purified OMVs containing oligomeric PorB.
• PorB from OMVs and bacteria targeted macrophage mitochondria.
• This targeting led to loss of mitochondrial membrane potential, cytochrome c release, caspase activation, and cell death.
• OMV-induced macrophage apoptosis was inhibited by a pan-caspase inhibitor.

Conclusions:

• Neisseria gonorrhoeae employs OMVs to deliver PorB to macrophage mitochondria.
• PorB induces apoptosis in macrophages by disrupting mitochondrial function.
• This mechanism contributes to N. gonorrhoeae's evasion of innate immunity.