The Haemophilus influenzae Hia autotransporter harbours two adhesive pockets that reside in the passenger domain and recognize the same host cell receptor
The Haemophilus influenzae Hia autotransporter harbours two adhesive pockets that reside in the passenger domain and recognize the same host cell receptor
复制标题
DOI：
10.1046/j.1365-2958.2002.03189.x
复制
发表时间：
2002-11-01
影响因子：
3.6
通讯作者：
St Geme, JW
中科院分区：
文献类型：
--
作者：
Laarmann, S;Cutter, D;St Geme, JW
流感嗜血杆菌是一种人类特有的病原体，也是世界范围内发病率的主要来源。这种微生物的感染始于鼻咽的定植，这一过程可能依赖于对呼吸道上皮的黏附。Hia自身转运蛋白是一组非分型流感嗜血杆菌菌株表达的主要粘附素，可促进多种人上皮细胞株的高水平黏附。在目前的研究中，我们发现Hia乘客结构域包含两个不同的结合口袋，其中一个在C-末端，另一个在N-末端。竞争分析表明，这两个结合口袋与相同的宿主细胞受体结构相互作用，尽管亲和力不同。进一步的实验证明，这两个结合域都是细菌完全黏附所必需的。这些观察结果让人想起真核细胞黏附分子，并突出了细菌黏附素的第一个例子，该黏附素具有两个结构域，参与与相同宿主细胞受体的二价相互作用。这种相互作用增加了亲和力，从而稳定了细菌对上皮表面的黏附，尽管有咳嗽、打喷嚏和粘液纤毛清除等物理力量。
Haemophilus influenzae is a human-specific pathogen and a major source of morbidity worldwide. Infection with this organism begins with colonization of the nasopharynx, a process that probably depends on adherence to respiratory epithelium. The Hia autotransporter protein is the major adhesin expressed by a subset of non-typeable H. influenzae strains and promotes high-level adherence to a variety of human epithelial cell lines. In the current study, we discovered that the Hia passenger domain contains two distinct binding pockets, including one at the C-terminal end and a second at the N-terminal end. Competition assays revealed that the two binding pockets interact with the same host cell receptor structure, although with differing affinities. Additional experiments demonstrated that both binding domains are required for full-level bacterial adherence. These observations are reminiscent of eukaryotic cell adhesion molecules and highlight the first example of a bacterial adhesin with two domains that participate in a bivalent interaction with identical host cell receptors. Such an interaction increases avidity, thus stabilizing bacterial adherence to the epithelial surface, despite physical forces such as coughing, sneezing and mucociliary clearance.