David S. Stephens

Neisseria meningitidis (Nm ) is a bacterial pathogen responsible for invasive meningococcal disease. Though typically colonizing the nasopharynx, multiple outbreaks of meningococcal urethritis were first reported in 2015–2016; outbreaks originally presumed to be caused by Neisseria gonorrhoeae ( Ng ). Genomic analysis revealed that the Nm isolates causing these outbreaks were a distinct clade, and had integrated gonococcal DNA at multiple genomic sites, including the gonococcal denitrification apparatus aniA–norB , a partial gonococcal operon of five genes containing isp D, and the acetylglutamate kinase gene argB with the adjacent gonococcal locus NGO0843 . The urethritis isolates had also deleted the group C capsule biosynthesis genes cssA/B/C and csc , resulting in loss of capsule. Collectively, these isolates form the N. meningitidis urethritis clade ( Nm UC). Genomic analysis of recent (2016–2022) Nm UC isolates revealed that the genomic features have been maintained in the clade, implying that they are important for Nm UC’s status as a urogenital pathogen. Furthermore, the analysis revealed the emergence of a sub-clade, designated Nm UC-B, phylogenetically separated from the earlier Nm UC-A. This sub-clade has integrated additional gonococcal alleles into the genome, including alleles associated with antimicrobial resistance. Nm UC continues to adapt to a urethral niche and evolve as a urogenital pathogen.