The role of type IV pilus retraction during the infection process of Neisseria gonorrhoeae

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The early stage of Neisseria gonorrhoeae infection, which causes gonorrhea, involves type IV pilus (tfp)-mediated attachment and the formation of bacterial microcolonies on epithelial cells. A key feature of tfp is their ability to retract, driven by the pilus retraction protein PilT. This retraction generates significant forces on host cells and neighboring bacteria. Previous studies suggested that tfp retraction force activates host cell signaling. This thesis hypothesizes that this force could activate nuclear factor kappa B (NF-κB), a central component of innate immunity signaling. Research using a p65-GFP-expressing epithelial cell line demonstrated that a retraction-deficient pilT mutant leads to significantly reduced NF-κB activation compared to wild-type bacteria. This reduction was linked to decreased transcription of NF-κB target genes and cytokine release. Notably, applying mechanical shear stress to infected host cells restored NF-κB activation levels to those induced by wild-type bacteria, indicating that retractile pili-generated mechanical forces are crucial for NF-κB activation. Live cell microscopy revealed that piliated wild-type Neisseria induce asynchronous NF-κB activation in infected cells, correlating with gonococcal microcolony formation. This research highlights the intricate relationship between N. gonorrhoeae pilus retraction, microcolony growth, and host cell signaling, leaving the potential influen