LAUSR

Introduction Mainly case reports have shown that N. meningitidis, typically a resident of the oropharynx and the causative agent of meningococcal meningitis and meningococcemia, is capable of invading and colonising the urogenital tract. This can result in urethritis, akin to the syndrome caused by N. gonorrhoeae, the etiologic agent of gonorrhoea. Recently, meningococcal strains associated with outbreaks of urethritis were reported to share genetic characteristics with gonococcus, raising the question of the extent to which these strains contain features that promote adaptation to the genitourinary niche, making them “gonococcus-like” and distinguishing them from other N. meningitidis. Methods A total of 31 urethritis-associated N. meningitidis, representing multiple serogroups and independently collected over a decade and 3 continents, underwent genome sequencing and analysis. The genomes were compared with serogroup-matched N. meningitidis strains isolated from carriage and invasive disease and N. gonorrhoeae strains isolated from men with urethritis. Results Intact nitrite reductase (AniA), disrupted factor-H binding protein (fHbp), and the lack of capsule are features previously speculated to promote urogenital colonisation. However, we found that a considerable number (n=11) of meningococcal urethritis isolates harbour mutations in AniA predicted to result in truncated peptides and a minority (n=4) of these isolates contained alleles associated with frameshifted fHbp. We noted substantial diversity in the capsule biosynthetic locus, including intact, disrupted, and absent capsules, indicating urogenital colonisation is possible across a range of capsular phenotypes. Conclusion The meningococcal urethritis strains in this study do not share the allelic patterns of AniA, fHbp, or the capsule locus previously reported for urethritis-associated N. meningitidis. The allelic patterns likely reflect diversity in the underlying meningococcal population, rather than novel adaptation to the urogenital tract.