The Neisseria meningitidis urethritis clade (NmUC) acts as a “chimeric pathogen” during infection of primary, human male, urethral epithelial cells

Background Clusters of male urethritis cases, caused by a novel clade of non-groupable Neisseria meningitidis (NmUC, “the clade”), have been reported globally. Genetic features unique to NmUC isolates include: the acquisition of the gonococcal denitrification loci, norB-aniA; a unique factor H binding protein (fHbp) variant; and loss of group C capsule and intrinsic lipooligosaccharide sialylation. We hypothesized that these characteristics might confer a colonization and survival advantage to NmUC during male urethral infection relative to non-clade group C Neisseria meningitidis. Methods NmUC, gonococcal, and non-clade meningococcal strains were comparatively evaluated in primary, human male, urethral epithelial cell (UEC) infection studies. Results NmUC strains were approximately six times 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 non-clade meningococcal strains. NmUC adherence to, invasion of, and survival within UECs was significantly decreased when host receptors known to mediate gonococcal or meningococcal interactions with epithelial cells were blocked. Infection studies indicated that fHbp contributes to clade survival independent of its ability to bind extracellular factor H, and 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.