Continuing genomic evolution of the Neisseria meningitidis cc11.2 urethritis clade, NmUC: a narrative review

• Type of Material: Article
• Authors: Emilio I. Rodriguez, Emory University; Yih-Ling Tzeng, Emory University; David Stephens, Emory University
• Language: English
• Date: 2023-10-01
• Publisher: Microbiology Society
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1099/mgen.0.001113
• Title of Journal or Parent Work: Microbial Genomics
• Volume: 9
• Issue: 10
• Grant/Funding Information: This work was supported in part by NIH grants R01AI127863, R21AI128313 and R21AI164733. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
• Keywords: Evolution, Molecular; Neisseria meningitidis; Urethritis; urogenital pathogen; Neisseria gonorrhoeae; Meningococcal Infections; Humans; Genomics; NmUC; genomic evolution; Gonorrhea; antimicrobial resistance
• Research Categories: Biology, Microbiology; Biology, Genetics

Abstract

Neisseria meningitidis (Nm) is a bacterial pathogen responsible for invasive meningococcal disease. Though typically coloniz-ing 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 ispD, 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 (NmUC). Genomic analysis of recent (2016–2022) NmUC isolates revealed that the genomic features have been maintained in the clade, implying that they are important for NmUC’s status as a urogenital pathogen. Furthermore, the analysis revealed the emergence of a sub-clade, designated NmUC-B, phylogenetically separated from the earlier NmUC-A. This sub-clade has integrated additional gonococcal alleles into the genome, including alleles associated with antimicrobial resistance. NmUC continues to adapt to a urethral niche and evolve as a urogenital pathogen.