Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA
Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA
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DOI：
10.1038/nmicrobiol.2016.188
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发表时间：
2017-01-01
影响因子：
28.3
通讯作者：
Haas, Rainer
中科院分区：
文献类型：
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作者：
Koeniger, Verena;Holsten, Lea;Haas, Rainer
幽门螺杆菌(Hp)携带CAG IV型分泌系统(CAG-T4SS)将细胞毒素相关抗原A(CagA)注入宿主细胞，与消化性溃疡疾病和胃腺癌有关。幽门螺杆菌的CagA转位是由CAG-T4SS的β1整合素相互作用介导的。然而，这一过程所必需的其他细胞受体或细菌外膜粘附素尚不清楚。在这里，我们利用癌胚抗原相关细胞黏附分子家族(CEACAMs)的特定成员作为宿主细胞受体，鉴定HopQ蛋白是真正的Hp粘附素。HopQ结合人CEACAM1、CEACAM3、CEACAM5或CEACAM6蛋白的氨基端IGV样结构域，从而使主要致病因子CagA能够转位到宿主细胞中。HopQ-CEACAM的相互作用具有极高的亲和力(K-D为23~268 nM)，不依赖于CEACAM的糖基化作用，这表明CEACAMs是Hp的真正蛋白质受体。我们的数据表明，HopQ-CEACAM相互作用有助于胃定植或幽门螺杆菌诱导的病理，尽管这种相互作用在体内的确切作用和功能后果仍未确定。
Helicobacter pylori (Hp) strains that carry the cag type IV secretion system (cag-T4SS) to inject the cytotoxin-associated antigen A (CagA) into host cells are associated with peptic ulcer disease and gastric adenocarcinoma. CagA translocation by Hp is mediated by beta 1 integrin interaction of the cag-T4SS. However, other cellular receptors or bacterial outer membrane adhesins essential for this process are unknown. Here, we identify the HopQ protein as a genuine Hp adhesin, exploiting defined members of the carcinoembryonic antigen-related cell adhesion molecule family (CEACAMs) as host cell receptors. HopQ binds the amino-terminal IgV-like domain of human CEACAM1, CEACAM3, CEACAM5 or CEACAM6 proteins, thereby enabling translocation of the major pathogenicity factor CagA into host cells. The HopQ-CEACAM interaction is characterized by a remarkably high affinity (K-D from 23 to 268 nM), which is independent of CEACAM glycosylation, identifying CEACAMs as bona fide protein receptors for Hp. Our data suggest that the HopQ-CEACAM interaction contributes to gastric colonization or Hp-induced pathologies, although the precise role and functional consequences of this interaction in vivo remain to be determined.