Poster Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

Neisseria Spp secretes extracellular vesicles to control innate immune responses (#107)

Pankaj Deo 1 , Eva Heinz 2 , Thomas Naderer 1
  1. Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia
  2. Department of Microbiology, Monash University, Melbourne, VIC, Australia

Neisseria gonorrhoeae causes the sexual transmitted disease gonorrhoea in more than 80 million people worldwide. Due to resistance to last-line drugs, gonorrhoea-associated inflammation and reproductive health damage are becoming increasingly difficult to treat.  N. gonorrhoeae is also a highly adapted commensal Gram-negative bacterium that has evolved sophisticated mechanisms to evade the adaptive immune system. It remains unclear, however, how they survive the innate immune attack by macrophages. We now show that Neisseria delivers several virulence factors using extracellular vesicles. We have established that the most abundant protein of these vesicles is the porin “PorB”, able to target host cell mitochondria and to induce cell death. By using live-cell imaging and super resolution microscopy, we show that macrophages take up Neisseria vesicles and that PorB escapes to the mitochondria. There, PorB sensitizes and induces apoptotic cell death, which allows Neisseria evasion of macrophages. In addition to cell death, we are currently investigating whether these vesicles also induce inflammatory immune responses, which are hallmarks of Neisseria infections. This will provide novel avenues to treat the pathological symptoms associated with gonorrhoea.