Acquisition of Gonococcal AniA-NorB Pathway by the Neisseria meningitidis Urethritis Clade Confers Denitrifying and Microaerobic Respiration Advantages for Urogenital Adaptation

Abstract

Neisseria meningitidis historically has been an infrequent and sporadic cause of urethritis and other urogenital infections.

Detection of Novel US Neisseria meningitidis Urethritis Clade Subtypes in Japan

“…Moreover, we included 3 ST23 N. meningitidis isolates (NM001, NM003, and NIID574) from Japan harboring the gonococcal aniA-norB locus ( 30 ), designated as J_NmUC-II ( Figure 1 ). The aniA-norB locus in the 3 ST11 J_NmUC isolates was 100% identical to that in US_NmUC meningococci ( 12 , 17 ), indicating the aniA-norB locus in the 3 J_NmUC strains was of gonococcal origin. In the 3 ST11 J_NmUC and 3 J_NmUC-II isolates, the aniA-norB locus was located between gpxA and NMB1624 genes ( Appendix 2 Figure 1), which was identical to that in US_NmUC N. meningitidis strains ( 12 ).…”

“…Moreover, if the meningococcal aniA gene was intact, expression was lower than that of gonococcal aniA genes ( 45 ). However, the gonococcal aniA-norB locus was not detected in some N. meningitidis isolates from patients with meningococcal urethritis ( 30 ), suggesting that acquisition of the gonococcal aniA-norB locus was advantageous ( 12 , 13 , 17 ) but not essential to cause urethritis.…”

“…Moreover, the factor H binding protein (fHbp), which binds to human factor H and inhibits the alternative complement activation pathway in the human immune system ( 16 ), was highly expressed in US_NmUC N. meningitidis isolates and might promote evasion from immune responses in the human urogenital tract ( 12 ). The most unique feature of US_NmUC meningococci is their acquisition of the N. gonorrhoeae denitrification apparatus that comprises gonococcal alleles encoding nitrate reductase AniA and nitric oxide reductase NorB and the intergenic promoter region, which confers survival in the urogenital tract ( 12 , 17 ).…”

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

“…A recent study showed that oxygen consumption, nitrite utilization, and NO production were significantly altered by the Ng AniA–NorB conversion in the Nm UC, resulting in different denitrifying aerobic and microaerobic growth of the Nm UC. Denitrification and microaerobic respiration were bolstered and protection against host-derived NO likely enhanced, supporting the Nm UC adaptation and survival in a microaerobic urogenital environment [38, 58]. These genes have been implicated in biofilm formation during natural gonococcal infection [59], and NorB also plays a significant role in protection against NO, produced by epithelial and phagocytic host cells encountered during infection.…”