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

Abstract

, 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, , 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 strains. Here, we analyzed the genomes of 39 diverse isolates associated with urethritis, collected independently over a decade and across three continents. In particular, we characterized the diversity of the nitrite reductase gene (), the factor H-binding protein gene (), 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 and and the presence of intact, disrupted, and absent capsule biosynthetic genes, indicating that urogenital colonization and urethritis caused by are possible across a range of meningococcal genotypes. Previously identified allelic patterns in urethritis-associated strains may reflect genetic diversity in the underlying meningococcal population rather than novel adaptation to the urogenital tract.

Applications of genomics to slow the spread of multidrug‐resistant Neisseria gonorrhoeae

“…The standard pigeonholing of these species—while a convenient shorthand—belies the clinical observations that not all the Gram negative diplococci that cause “gonorrhea‐like” symptoms are N. gonorrhoeae . Meningococcus and Neisseria lactamica have been isolated in urethritis cases, and a recent outbreak of meningococcal urethritis renewed interest in the question of whether adaptation to the urogenital niche may happen periodically . N. gonorrhoeae is not as diverse as other Neisseria (Fig.…”

“…Multiple N. gonorrhoeae lineages have acquired porA sequences from N. meningitidis , replacing the gonococcal porA pseudogene that is occasionally used for diagnostics . Exchange among Neisseria species is not unidirectional, and urethritis‐associated N. meningitidis isolates contain recombinant tracts originating from N. gonorrhoeae …”

Neisseria meningitidis urethritis: synthesis of published data

“…Neisseria meningitidis has been isolated from anogenital sites and has been documented as a cause of anogenital infection in many publications . The first report published in 1942 by Carpenter and Charles described seven isolates of NM among 103 urogenital isolates of Neisseria .…”

“…In heterosexuals, most cases occur via orogenital transmission, with the nasopharynx as the major reservoir . In these cases, nongroupable NM (multi‐gene deletion at the capsule synthesis locus) were isolated.…”

“…Neisseria meningitidis urethritis raises major public health issues because of: increasing prevalence of ST11 worldwide; a reported “notable genetic diversity” in the meningococci; the difficulty to diagnose NM urethritis conventionally; the diversity of the subgroups involved and their respective sexual behaviors; an increase in NG resistance and a failure in oropharyngeal NG clearance . Consequently, increases in the likelihood of NG/NM nasopharynx colonization would provide an opportunity for further genetic exchange between the two pathogens and for emergence of new variants.…”