Nap genes in Neisseria spp.

Neisseria gonorrhoeae is a human-specific pathogen that causes the important sexually transmitted infection, gonorrhoea, an inflammatory condition of the genitourinary tract. The bacterium is closely related to the meningococcus, a leading cause of bacterial meningitis. Both these invasive bacterial species undergo autolysis when in the stationary phase of growth. Autolysis is a form of programmed cell death (PCD) which is part of the life cycle of remarkably few bacteria and poses an evolutionary conundrum as altruistic death provides no obvious benefit for single-celled organisms. Here, we searched for genes present in these 2 invasive species but not in other members of the Neisseria genus. We identified a ~3.4 kb horizontally acquired region, we termed the nap island, which is largely restricted to the gonococcus and meningococcus. The nap island in the gonococcus encodes 3 cationic, bacteriocin-like peptides which have no detectable antimicrobial activity. Instead, the gonococcal Neisseria autolysis peptides (Naps) promote autolytic cell death when bacteria enter the stationary phase of growth. Furthermore, strains lacking the Naps exhibit reduced autolysis in assays of PCD. Expression of Naps is likely to be phase variable, explaining how PCD could have arisen in these important human pathogens. NapC also induces lysis of human cells, so the peptides are likely to have multiple roles during colonisation and disease. The acquisition of the nap island contributed to the emergence of PCD in the gonococcus and meningococcus and potentially to the appearance of invasive disease in Neisseria spp.

淋病奈瑟菌（Neisseria gonorrhoeae）是一种人类专属病原体，可引发重要的性传播感染——淋病，即泌尿生殖道炎症。该菌与脑膜炎奈瑟菌（meningococcus）亲缘关系密切，后者是细菌性脑膜炎的主要致病原。这两种侵袭性细菌在生长稳定期均会发生自溶现象。自溶属于程序性细胞死亡（programmed cell death, PCD）的一种形式，仅在极少数细菌的生命周期中存在；这种利他性死亡对单细胞生物并无明显益处，因此构成了一道进化谜题。本研究针对这两种侵袭性物种中存在、但奈瑟菌属（Neisseria）其他成员不具备的基因进行了检索。我们发现了一段约3.4 kb的水平获得基因组区域，将其命名为nap岛（nap island），该区域主要局限于淋球菌和脑膜炎奈瑟菌。淋球菌中的nap岛编码3种阳离子类细菌素肽，未检测到其具有抗菌活性。与之相反，淋球菌奈瑟菌自溶肽（Neisseria autolysis peptides, Naps）可在细菌进入生长稳定期时促进自溶型细胞死亡。此外，缺失Naps的菌株在程序性细胞死亡实验中表现出自溶能力降低。Naps的表达大概率具有相变异（phase variable）特性，这一特性解释了为何这类重要人类病原体中会出现程序性细胞死亡。NapC还可诱导人类细胞裂解，因此这类肽可能在定植与致病过程中发挥多重作用。nap岛的获取推动了淋球菌和脑膜炎奈瑟菌中程序性细胞死亡的出现，并可能促成了奈瑟菌属物种侵袭性疾病的产生。