# Acquisition of gonococcal denitrification apparatus in the Neisseria meningitidis urethritis clade

> **NIH NIH R21** · EMORY UNIVERSITY · 2022 · $233,792

## Abstract

Project Summary
Neisseria meningitidis is carried in the nasopharynx asymptomatically by up to 5-10% of the human population
and remains a leading cause of meningitis and rapidly fatal sepsis, usually in otherwise healthy individuals.
Historically, N. meningitidis has not been a significant sexually transmitted pathogen. However, since 2015
recent outbreaks of sexually transmitted meningococcal urethritis have occurred, primarily, in heterosexual
males in over thirteen US states, the UK, and Vietnam. Unlike previous sporadic cases of meningococcal
urethritis, these urethritis cases are all caused by a capsule-defective meningococcal clade belonging to the
hyper-invasive cc11.2 lineage. This clade of N. meningitidis, like N. gonorrhoeae, causes male urethritis in
unprecedented numbers in communities, can also be isolated from the pharynx and rectal tract, and can cause
meningococcemia and meningitis, as well as other mucosal infections (neonatal conjunctivitis). Whereas isolated
cases of urogenital colonization and urethritis caused by a range of meningococcal genotypes are reported, no
other genotype has caused widespread urethritis outbreaks. These urethritis outbreaks suggest that this 11.2
lineage clade has acquired novel genetic and, thus, phenotypic changes that allow it to effectively colonize the
urogenital tract, to adapt to local innate immune responses, and to cause urogenital tract disease. In support of
this hypothesis, we discovered that all isolates of N. meningitidis urethritis clade, from multiple states and
globally, but not sporadic meningococcal urethritis isolates, have the distinct N. gonorrhoeae denitrification
apparatus - the gonococcal nitrite reductase, AniA, and the gonococcal nitric oxide (NO) reductase, NorB. This
precise chromosomal gene conversion event has also endowed the clade with the gonococcal regulatory region
that separates the divergent transcripts encoding aniA and norB. This aniA-norB conversion appears to provide
a major adaptation to N. meningitidis for the oxygen-limited microaerobic/anaerobic urogenital environment and
allowing emergence of this urethrotropic meningococcal clade. In two Specific Aims, we seek to define the unique
regulatory and physiological traits conferred to this meningococcal clade through the gonococcal aniA-norB gene
conversion event. In Aim 1, the unique hybrid transcriptional regulatory network, consisting of multiple
meningococcal regulators controlling the divergently transcribed gonococcal aniA and norB promoters, will be
examined in detail to define, new and critical, cis and trans regulatory elements in this clade. Global transcription
profiles affected by the gene conversion in the clade will be examined using RNA-seq. In Aim 2, we will determine
the impact of the gonococcal denitrification conversion on phenotypes important in urogenital pathogenesis:
microaerobic growth, NO susceptibility and utilization, and defense against NO-mediated immune responses.
Successful comp...

## Key facts

- **NIH application ID:** 10448441
- **Project number:** 5R21AI164733-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jennifer L Edwards
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $233,792
- **Award type:** 5
- **Project period:** 2021-07-12 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448441

## Citation

> US National Institutes of Health, RePORTER application 10448441, Acquisition of gonococcal denitrification apparatus in the Neisseria meningitidis urethritis clade (5R21AI164733-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10448441. Licensed CC0.

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