Neisseria meningitidis NhhA is a multifunctional trimeric autotransporter adhesin
Neisseria meningitidis NhhA is a multifunctional trimeric autotransporter adhesin
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DOI：
10.1111/j.1365-2958.2006.05261.x
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发表时间：
2006-08-01
影响因子：
3.6
通讯作者：
Arico, Beatrice
中科院分区：
文献类型：
--
作者：
Scarselli, Maria;Serruto, Davide;Arico, Beatrice
NhhA，Neisseria hia/hsf homologue，或GNA 0992，是脑膜炎奈瑟氏菌的寡聚外膜蛋白，最近被包括在三聚体自身转运粘附素家族中。在这项研究中，我们提出了这种蛋白质的结构和功能特性。通过在大肠杆菌中表达NhhA的全长基因、缺失突变体和嵌合蛋白，我们证明了最后72个C-末端残基能够使N-末端蛋白结构域三聚化并定位于细菌表面。此外，我们还研究了NhhA在细菌-宿主相互作用事件中的可能作用。我们在体外评估重组纯化的NhhA结合人上皮细胞以及层粘连蛋白和硫酸乙酰肝素的能力。此外，我们还证明了E.表达NhhA的大肠杆菌菌株能够粘附于上皮细胞，并且在脑膜炎球菌同基因MC 58 Δ NhhA突变体中观察到降低的粘附。我们的结论是，该蛋白是一个多功能的粘附素，能够促进细菌粘附宿主细胞和细胞外基质成分。总的来说，我们的研究结果强调了NhhA在脑膜炎球菌发病机制中的假定作用，并确定其结构和功能属于新兴的细菌自转运粘附素与三聚体结构。
NhhA, Neisseria hia/hsf homologue, or GNA0992, is an oligomeric outer membrane protein of Neisseria meningitidis, recently included in the family of trimeric autotransporter adhesins. In this study we present the structural and functional characterization of this protein. By expressing in Escherichia coli the full-length gene, deletion mutants and chimeric proteins of NhhA, we demonstrated that the last 72 C-terminal residues are able to allow trimerization and localization of the N-terminal protein domain to the bacterial surface. In addition, we investigated on the possible role of NhhA in bacterial-host interaction events. We assessed in vitro the ability of recombinant purified NhhA to bind human epithelial cells as well as laminin and heparan sulphate. Furthermore, we shown that E. coli strain expressing NhhA was able to adhere to epithelial cells, and observed a reduced adherence in a meningococcal isogenic MC58 Delta NhhA mutant. We concluded that this protein is a multifunctional adhesin, able to promote the bacterial adhesion to host cells and extracellular matrix components. Collectively, our results underline a putative role of NhhA in meningococcal pathogenesis and ascertain its structural and functional belonging to the emerging group of bacterial autotransporter adhesins with trimeric architecture.