Genomic Characterization of Urethritis-Associated Neisseria meningitidis Shows that a Wide Range of N. meningitidis Strains Can Cause Urethritis

Abstract

Neisseria meningitidis, typically a resident of the oro- or nasopharynx and the causative agent of meningococcal meningitis and meningococcemia, is capable of invading and colonizing the urogenital tract. This can result in urethritis, akin to the syndrome caused by its sister species, N. gonorrhoeae, the etiologic agent of gonorrhea. Recently, meningococcal strains associated with outbreaks of urethritis were reported to share genetic characteristics with the 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 strains. Here, we analyzed the genomes of 39 diverse N. meningitidis isolates associated with urethritis, collected independently over a decade and across three continents. In particular, we characterized the diversity of the nitrite reductase gene (aniA), the factor H-binding protein gene (fHbp), and the capsule biosynthetic locus, all of which are loci previously suggested to be associated with urogenital colonization. We observed notable diversity, including frameshift variants, in aniA and fHbp and the presence of intact, disrupted, and absent capsule biosynthetic genes, indicating that urogenital colonization and urethritis caused by N. meningitidis are possible across a range of meningococcal genotypes. Previously identified allelic patterns in urethritis-associated N. meningitidis strains may reflect genetic diversity in the underlying meningococcal population rather than novel adaptation to the urogenital tract.

Keywords: Neisseria gonorrhoeae; Neisseria meningitidis; bacterial genomics; urethritis.

FIG 1

Core genome phylogeny and genomic characterization of aniA, fHbp, and capsular region A of urethritis-associated N. meningitidis and N. lactamica isolates. For aniA and fHbp, blue shading indicates a full gene product and red shading indicates a truncated gene product. Alleles associated with truncated genes and alleles associated with full genes found in three or more isolates are specifically denoted in the key on the left; all other alleles were grouped into the “other” category. aniA alleles 23 and 204 are putatively gonococcal in origin. For capsule region A, csx variants which determine the serogroup (where csx can be csb, csc, csy, or cszD), the presence of either cssE or cssF, and capsule gene disruption via insertion sequence or frameshift are specified by the colors and symbols in the key. *, strains predicted to encode capsules; unshaded boxes, missing genes. Clonal complexes are indicated along the right, with asterisks indicating no associated clonal complex.