The Neisseria meningitidis Urethritis Clade (NmUC) Acts as a "Chimeric Pathogen" During Infection of Primary, Human Male, Urethral Epithelial Cells

Background Male urethritis cases, caused by a novel clade of nongroupable Neisseria meningitidis (NmUC, "the clade"), have been reported globally.Methods To test whether genetic features unique to NmUC confer a colonization and survival advantage to NmUC during urethral infection, NmUC, gonococcal, and nonclade meningococcal strains were comparatively evaluated in primary, human male, urethral epithelial cell (UEC) infection studies.Results NmUC strains were more invasive in UECs than the gonococcal strains tested, which could not be attributed to loss of capsule expression alone. Whereas gonococci and NmUC strains survived and proliferated within UECs, negligible survival was observed for nonclade meningococcal strains. NmUC infection of UECs was impaired when host receptors known to mediate gonococcal or meningococcal interactions with epithelial cells were blocked. We found that fHbp contributes to clade survival independent of its ability to bind extracellular factor H, and that the gonococcal denitrification pathway, particularly NorB, plays an important role in promoting clade intracellular survival.Conclusions Whereas mechanisms used by NmUC to infect UECs are shared with other neisserial strains, hybrid mechanisms unique to the clade also mediate infection and allow adaptation to the male urethra. Thus, NmUC is a "chimeric pathogen," displaying facets of gonococcal and meningococcal pathogenesis. We show that the mechanisms used by a novel clade of nongroupable Neisseria meningitidis to cause urethritis are shared with Neisseria gonorrhoeae, but hybrid mechanisms unique to this clade also mediate infection and allow adaptation to the male urethra.