Neisseria gonorrhoeae is the causative agent of gonorrhea, a common sexually transmitted infection. In this study, I characterize the fit locus and its role in host–pathogen interactions. Mutations in the fit locus increased the rate of bacterial transcytosis across polarized human cell monolayers and impaired pilE intragenic recombination during infection. The fit locus encodes two proteins, FitA and FitB. FitA is a ribbon–helix–helix DNA-binding protein that forms a heterooctomeric complex with FitB and binds a specific promoter sequence with markedly increased affinity compared to FitA alone. Structural analysis confirmed the DNA-binding mechanism and revealed a putative PIN domain in FitB. Together, these findings suggest that the fit locus promotes pilE recombination during transcytosis, contributing to immune evasion and influencing bacterial trafficking and replication.
