Schielke Stephanie, Huebner Claudia, Spatz Carolin, Nägele Virginie, Ackermann Nikolaus, Frosch Matthias, Kurzai Oliver, Schubert-Unkmeir Alexandra
University of Würzburg, Institute of Hygiene and Microbiology, Würzburg, Germany.
Mol Microbiol. 2009 May;72(4):1054-67. doi: 10.1111/j.1365-2958.2009.06710.x. Epub 2009 Apr 21.
Two closely related pathogenic species have evolved in the genus Neisseria: N. meningitidis and N. gonorrhoeae, which occupy different host niches and cause different clinical entities. In contrast to the pathogen N. gonorrhoeae, N. meningitidis is a commensal and only rarely becomes invasive. Little is known about the genetic background of the entirely different lifestyles in these closely related species. Meningococcal NMB1843 encodes a transcriptional regulator of the MarR family. The gonococcal homologue FarR regulates expression of farAB, mediating fatty acid resistance. We show that NmFarR also directly interacts with NmfarAB. Yet, by contrast to N. gonorrhoeae, no significant sensitivity to fatty acids was observed in a DeltafarR mutant due to intrinsic resistance of meningococci. Further analyses identified an NmFarR-repressed protein absent from N. gonorrhoeae. This protein is the meningococcus-specific adhesin and vaccine component NadA that has most likely been acquired by horizontal gene transfer. NmFarR binds to a 16 base pair palindromic repeat within the nadA promoter. De-repression of nadA resulted in significantly higher association of a DeltafarR strain with epithelial cells. Hence NmFarR has gained control over a meningococcus-specific gene involved in host colonization and thus contributed to divergent niche adaptation in pathogenic Neisseriae.
脑膜炎奈瑟菌和淋病奈瑟菌，它们占据不同的宿主生态位并导致不同的临床病症。与病原体淋病奈瑟菌不同，脑膜炎奈瑟菌是一种共生菌，很少发生侵袭性感染。对于这些密切相关物种中完全不同生活方式的遗传背景知之甚少。脑膜炎奈瑟菌NMB1843编码一种MarR家族的转录调节因子。淋病奈瑟菌的同源物FarR调节farAB的表达，介导脂肪酸抗性。我们发现NmFarR也直接与NmfarAB相互作用。然而，与淋病奈瑟菌不同，由于脑膜炎奈瑟菌的固有抗性，在DeltafarR突变体中未观察到对脂肪酸的显著敏感性。进一步分析确定了淋病奈瑟菌中不存在的一种NmFarR抑制蛋白。该蛋白是脑膜炎奈瑟菌特异性黏附素和疫苗成分NadA，很可能是通过水平基因转移获得的。NmFarR与nadA启动子内的一个16碱基对回文重复序列结合。nadA的去抑制导致DeltafarR菌株与上皮细胞的结合显著增加。因此，NmFarR已获得对一个参与宿主定植的脑膜炎奈瑟菌特异性基因的控制，从而促进了致病性奈瑟菌在不同生态位的适应。
