Tzeng Yih-Ling, Esposito Danillo L A, Nederveld Andrew G, Hardison Rachael L, Carter Alexandria M, Stephens David S, Norris Turner Abigail, Bazan Jose A, Edwards Jennifer L
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital.
J Infect Dis. 2025 Jul 11;231(6):1478-1488. doi: 10.1093/infdis/jiae604.
Male urethritis cases, caused by a novel clade of nongroupable Neisseria meningitidis (NmUC, "the clade"), have been reported globally.
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.
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.
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.
由新型不可分组脑膜炎奈瑟菌（NmUC，“该分支”）引起的男性尿道炎病例已在全球范围内被报道。
为了测试NmUC特有的遗传特征是否在尿道感染期间赋予NmUC定植和生存优势，在原发性人类男性尿道上皮细胞（UEC）感染研究中对NmUC、淋球菌和非分支脑膜炎奈瑟菌菌株进行了比较评估。
NmUC菌株在UEC中的侵袭性比所测试的淋球菌菌株更强，这不能仅归因于荚膜表达的丧失。虽然淋球菌和NmUC菌株在UEC内存活并增殖，但非分支脑膜炎奈瑟菌菌株的存活情况可忽略不计。当已知介导淋球菌或脑膜炎奈瑟菌与上皮细胞相互作用的宿主受体被阻断时，UEC的NmUC感染受到损害。我们发现，fHbp有助于该分支的存活，与其结合细胞外因子H的能力无关，并且淋球菌反硝化途径，特别是NorB，在促进该分支细胞内存活中起重要作用。
虽然NmUC感染UEC所使用的机制与其他奈瑟菌菌株相同，但该分支特有的混合机制也介导感染并使其适应男性尿道。因此，NmUC是一种“嵌合病原体”，表现出淋球菌和脑膜炎奈瑟菌发病机制的特点。
