National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Mol Microbiol. 2012 Oct;86(2):246-57. doi: 10.1111/mmi.12002. Epub 2012 Sep 7.
Two pathogenic species within the genus Neisseria cause the diseases gonorrhoea and meningitis. While vaccines are available to protect against four N. meningitidis serogroups, there is currently no commercial vaccine to protect against serogroup B or against N. gonorrhoeae. Moreover, the available vaccines have significant limitations and with antibiotic resistance becoming an alarming issue, the search for effective vaccine targets to elicit long-lasting protection against Neisseria species is becoming more urgent. One strategy for vaccine development has targeted the neisserial iron import systems. Without iron, the Neisseriae cannot survive and, therefore, these iron import systems tend to be relatively well conserved and are promising vaccine targets, having the potential to offer broad protection against both gonococcal and meningococcal infections. These efforts have been boosted by recent reports of the crystal structures of the neisserial receptor proteins TbpA and TbpB, each solved in complex with human transferrin, an iron binding protein normally responsible for delivering iron to human cells. Here, we review the recent structural reports and put them into perspective with available functional studies in order to derive the mechanism(s) for how the pathogenic Neisseriae are able to hijack human iron transport systems for their own survival and pathogenesis.
属内的两种致病性物种淋病奈瑟菌和脑膜炎奈瑟菌会引起淋病和脑膜炎。虽然有针对脑膜炎奈瑟菌四个血清群的疫苗来预防疾病，但目前还没有针对血清群 B 或淋病奈瑟菌的商业疫苗。此外，现有的疫苗有明显的局限性，而且随着抗生素耐药性成为一个令人担忧的问题，寻找有效的疫苗靶点来引发针对奈瑟菌属的持久保护变得更加紧迫。疫苗开发的一种策略是针对奈瑟菌的铁摄取系统。没有铁，奈瑟菌就无法生存，因此，这些铁摄取系统往往相对保守，是有前途的疫苗靶点，有可能对淋病奈瑟菌和脑膜炎奈瑟菌感染提供广泛的保护。最近报道了奈瑟菌受体蛋白 TbpA 和 TbpB 的晶体结构，这两种蛋白都与人类转铁蛋白结合，而转铁蛋白是一种通常负责将铁输送到人类细胞的铁结合蛋白，这一进展促进了这些努力。在这里，我们综述了最近的结构报告，并结合现有功能研究进行了分析，以推导出致病性奈瑟菌如何能够劫持人类铁转运系统来维持自身生存和发病机制的机制。
