Expression of CEACAM1 or CEACAM5 in AZ‐521 cells restores the type IV secretion deficiency for translocation of CagA by Helicobacter pylori
Expression of CEACAM1 or CEACAM5 in AZ‐521 cells restores the type IV secretion deficiency for translocation of CagA by Helicobacter pylori
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AZâ521 细胞中 CEACAM1 或 CEACAM5 的表达可恢复幽门螺杆菌 CagA 易位的 IV 型分泌缺陷
DOI：
10.1111/cmi.12965
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发表时间：
2019
影响因子：
3.4
通讯作者：
Backert
中科院分区：
文献类型：
--
作者：
Tegtmeyer;Harrer;Schmitt;Singer;Backert
幽门螺杆菌是一种重要的致病菌，可引起胃炎、消化性溃疡和胃恶性肿瘤等多种疾病。主要的毒力因子包括空泡细胞毒素VacA和细胞毒素相关基因致病岛（cagPAI）编码的IV型分泌系统（T4 SS）。T4 SS效应蛋白CagA可以易位到AGS和其他胃上皮细胞中，然后通过c-Src和c-Abl酪氨酸激酶磷酸化以劫持信号网络。十二指肠细胞系AZ-521最近被引入作为新的模型系统，以研究VacA依赖性方式的CagA递送和磷酸化。相比之下，我们发现AZ-521细胞在注射CagA时表现出T4 SS功能不全表型，这代表了第一个报道的具有显著T4 SS缺陷的胃肠道细胞系。我们认为这种缺陷可能是由于T4 SS受体整合素-β 1或癌胚抗原相关细胞粘附分子（CEACAMs）的不平衡共表达造成的，这些分子最近被描述为新分子H。幽门感受器我们证明AZ-521细胞容易表达整合素-β1，但整合素-β 1构建体的过表达不能恢复T4 SS缺陷。我们进一步表明AZ-521细胞缺乏CEACAMs的表达。我们证明，在AZ-521细胞中基因导入CEACAM 1或CEACAM 5，但不导入CEACAM 6，足以允许注射CagA并通过H磷酸化。在AGS细胞模型中观察到幽门程度。感染的AZ-521细胞中CEACAM 1或CEACAM 5的表达也伴随着细胞骨架蛋白纽蛋白和corptin的酪氨酸去磷酸化，这是H. pylori感染的AGS细胞我们的研究结果表明，CagA存在整合素β1和CEACAM 1或CEACAM 5依赖的T4 SS递送途径，这显然不依赖于VacA。在感染H. pylori在细菌T4 SS世界中是一个独特的特征。对这些T4 SS功能的进一步详细研究将有助于更好地理解细菌病原体的感染策略。
Helicobacter pylorirepresents an important pathogen involved in diseases ranging from gastritis, peptic ulceration, to gastric malignancies. Prominent virulence factors comprise the vacuolating cytotoxin VacA and the cytotoxin‐associated genes pathogenicity island (cagPAI)‐encoded type IV secretion system (T4SS). The T4SS effector protein CagA can be translocated into AGS and other gastric epithelial cells followed by phosphorylation through c‐Src and c‐Abl tyrosin kinases to hijack signalling networks. The duodenal cell line AZ‐521 has been recently introduced as novel model system to investigate CagA delivery and phosphorylation in a VacA‐dependent fashion. In contrast, we discovered that AZ‐521 cells display a T4SS incompetence phenotype for CagA injection, which represents the first reported gastrointestinal cell line with a remarkable T4SS defect. We proposed that this deficiency may be due to an imbalanced coexpression of T4SS receptor integrin‐β1or carcinoembryonic antigen‐related cell adhesion molecules (CEACAMs), which were described recently as novelH. pylorireceptors. We demonstrate that AZ‐521 cells readily express integrin‐β1, but overexpression of integrin‐β1constructs did not restore the T4SS defect. We further show that AZ‐521 cells lack the expression of CEACAMs. We demonstrate that genetic introduction of either CEACAM1 or CEACAM5, but not CEACAM6, in AZ‐521 cells is sufficient to permit injection and phosphorylation of CagA byH. pylorito degrees observed in the AGS cell model. Expression of CEACAM1 or CEACAM5 in infected AZ‐521 cells was also accompanied by tyrosine dephosphorylation of the cytoskeletal proteins vinculin and cortactin, a hallmark ofH. pylori‐infected AGS cells. Our results suggest the existence of an integrin‐β1‐ and CEACAM1‐ or CEACAM5‐dependent T4SS delivery pathway for CagA, which is clearly independent of VacA. The presence of two essential host protein receptors during infection withH. pylorirepresents a unique feature in the bacterial T4SS world. Further detailed investigation of these T4SS functions will help to better understand infection strategies by bacterial pathogens.
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幽门螺杆菌感染 AZ-521 细胞揭示 IV 型分泌缺陷和不依赖 VacA 的 CagA 磷酸化
影响因子：
4.3
作者：
Nicole Tegtmeyer;S. Backert
通讯作者：
S. Backert
影响因子：
29.4
作者：
Tammer, Ina;Brandt, Sabine;Backert, Steffen
通讯作者：
Backert, Steffen
液泡 ATP 酶质子泵存在于幽门螺杆菌诱导的细胞内液泡上。
影响因子：
3
作者：
E. Papini;E. Gottardi;B. Satin;M. de Bernard;P. Massari;J. Telford;R. Rappuoli;S. Sato;C. Montecucco
通讯作者：
C. Montecucco
影响因子：
7
作者：
Yahiro K;Akazawa Y;Nakano M;Suzuki H;Hisatune J;Isomoto H;Sap J;Noda M;Moss J;Hirayama T
通讯作者：
Hirayama T
影响因子：
6.7
作者：
Zhang XS;Tegtmeyer N;Traube L;Jindal S;Perez-Perez G;Sticht H;Backert S;Blaser MJ
通讯作者：
Blaser MJ