Grant: Project Grant

Neisseria gonorrhoeae has re-emerged as a global public health concern as it now causes nearly 100 million new infections each year and isolates have emerged that are resistant to all clinically-relevant antibiotics, prompting the US Center for Disease Control to name it as one of three 'urgent' microbial threats. The success of this organism is attributable in part to its capacity to colonize the female genital tract without obvious clinical manifestation, allowing it to persist undetected as it is spread to sexual partners. Consistent with this, N. gonorrhoeae does not express factors with overt virulent potential, but instead exhibits a lifestyle intent on avoiding and actively subverting immune detection. In this context, disease arises when the innate immune system eventually recognizes and responds to the infection with an overzealous neutrophil-based inflammatory response that damages the mucosal tissues. However, inexplicable in this context, this innate response does not lead to an adaptive immune response, so infected individuals remain susceptible to re-infection by even closely-related strains. This research project aims to understand the fine balance between immunity and immunopathogenesis in the context of N. gonorrhoeae infection, with a specific focus on the contribution of a bacterial-derived metabolite that we have recently discovered to have both immune modulatory and immune stimulatory properties.