A New Family of Secreted Toxins in Pathogenic Neisseria Species

The genus Neisseria includes both commensal and pathogenic species which are genetically closely related. However, only meningococcus and gonococcus are important human pathogens. Very few toxins are known to be secreted by pathogenic Neisseria species. Recently, toxins secreted via type V secretion system and belonging to the widespread family of contact-dependent inhibition (CDI) toxins have been described in numerous species including meningococcus. In this study, we analyzed loci containing the maf genes in N. meningitidis and N. gonorrhoeae and proposed a novel uniform nomenclature for maf genomic islands (MGIs). We demonstrated that mafB genes encode secreted polymorphic toxins and that genes immediately downstream of mafB encode a specific immunity protein (MafI). We focused on a MafB toxin found in meningococcal strain NEM8013 and characterized its EndoU ribonuclease activity. maf genes represent 2% of the genome of pathogenic Neisseria, and are virtually absent from non-pathogenic species, thus arguing for an important biological role. Indeed, we showed that overexpression of one of the four MafB toxins of strain NEM8013 provides an advantage in competition assays, suggesting a role of maf loci in niche adaptation.

奈瑟菌属（Neisseria）涵盖遗传关系紧密的共生菌株与致病菌株，但该属中仅脑膜炎奈瑟菌（meningococcus）与淋病奈瑟菌（gonococcus）为重要的人类致病菌。目前已知致病奈瑟菌分泌的毒素种类极少。近期研究在包括脑膜炎奈瑟菌在内的多个物种中，发现了通过V型分泌系统（type V secretion system）分泌、隶属于广泛分布的接触依赖型抑制（contact-dependent inhibition, CDI）毒素家族的毒素。本研究对脑膜炎奈瑟菌与淋病奈瑟菌中携带maf基因的基因座展开分析，并为maf基因组岛（maf genomic islands, MGIs）提出了一套全新的统一命名规范。我们证实，mafB基因编码分泌型多态性毒素，且mafB基因下游紧邻的基因编码特异性免疫蛋白MafI。本研究聚焦于脑膜炎奈瑟菌菌株NEM8013中的一款MafB毒素，并对其EndoU核糖核酸酶（EndoU ribonuclease）活性进行了表征。maf基因占致病奈瑟菌基因组的约2%，且几乎不存在于非致病奈瑟菌物种中，这提示其具备重要的生物学功能。实验结果表明，过表达菌株NEM8013的四款MafB毒素之一，可在竞争实验中获得竞争优势，进而证明maf基因座在生态位适应过程中发挥了关键作用。