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The Neisseria meningitidis Urethritis Clade (NmUC) Acts as a "Chimeric Pathogen" During Infection of Primary, Human
Yih-Ling Tzeng1, Danillo L A Esposito2, Andrew G Nederveld2
1Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Background:
Male urethritis cases, caused by a novel clade of nongroupable Neisseria meningitidis (NmUC, "the clade"), have been reported globally.
Methods:
To test whether genetic features unique to NmUC confer a colonization and survival advantage to NmUC during urethral infection, NmUC, gonococcal, and nonclade meningococcal strains were comparatively evaluated in primary, human male, urethral epithelial cell (UEC) infection studies.
Results:
NmUC strains were more invasive in UECs than the gonococcal strains tested, which could not be attributed to loss of capsule expression alone. Whereas gonococci and NmUC strains survived and proliferated within UECs, negligible survival was observed for nonclade meningococcal strains. NmUC infection of UECs was impaired when host receptors known to mediate gonococcal or meningococcal interactions with epithelial cells were blocked. We found that fHbp contributes to clade survival independent of its ability to bind extracellular factor H, and that the gonococcal denitrification pathway, particularly NorB, plays an important role in promoting clade intracellular survival.
Conclusions:
Whereas mechanisms used by NmUC to infect UECs are shared with other neisserial strains, hybrid mechanisms unique to the clade also mediate infection and allow adaptation to the male urethra. Thus, NmUC is a "chimeric pathogen," displaying facets of gonococcal and meningococcal pathogenesis.
Insights
Novel Neisseria meningitidis (NmUC) strains, causing urethritis, exhibit unique genetic traits for enhanced survival and invasion in male urethral cells. These "chimeric pathogens" blend gonococcal and meningococcal pathogenic features.
Area of Science:
- Microbiology
- Pathogenesis
- Infectious Diseases
Background:
- Novel clade of non-groupable Neisseria meningitidis (NmUC) identified globally causing male urethritis.
- NmUC possesses unique genetic features: gonococcal norB-aniA loci, a distinct fHbp variant, and loss of capsule/sialylation.
- Hypothesized NmUC genetic traits confer colonization and survival advantages in male urethral infections.
Purpose of the Study:
- To investigate the colonization and survival advantage of NmUC in male urethral infections.
- To compare NmUC with gonococcal and non-clade meningococcal strains in human male urethral epithelial cells (UECs).
Main Methods:
- Comparative evaluation of NmUC, gonococcal, and non-clade meningococcal strains.
- Infection studies using primary human male urethral epithelial cells (UECs).
- Analysis of adherence, invasion, and intracellular survival mechanisms.
Main Results:
- NmUC strains showed significantly higher invasiveness in UECs compared to gonococcal strains.
- NmUC and gonococcal strains demonstrated survival and proliferation within UECs, unlike non-clade meningococcal strains.
- Factor H binding protein (fHbp) and the norB gene were crucial for NmUC intracellular survival and adaptation.
Conclusions:
- NmUC utilizes shared neisserial infection mechanisms alongside unique hybrid mechanisms for male urethral adaptation.
- NmUC acts as a 'chimeric pathogen,' integrating gonococcal and meningococcal pathogenic characteristics.
- These adaptations facilitate NmUC's success in the male urethral environment.
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