Bourzac Kevin M, Satkamp Laura A, Guillemin Karen
Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
Infect Immun. 2006 May;74(5):2537-43. doi: 10.1128/IAI.74.5.2537-2543.2006.
Helicobacter pylori infects nearly half the world's population and is associated with a spectrum of gastric maladies. Infections with cytotoxin-associated gene pathogenicity island (cag PAI)-containing strains are associated with an increased risk for gastric cancer. The cag PAI contains genes encoding a type IV secretion system (T4SS) and a delivered effector, CagA, that becomes tyrosine phosphorylated upon delivery into host cells and initiates changes in cell signaling. Although some cag PAI genes have been shown to be required for CagA delivery, a subset of which are homologues of T4SS genes from Agrobacterium tumefaciens, the majority have no known function or homologues. We have performed a detailed investigation of one such cag PAI protein, CagN, which is encoded by the gene HP0538. Our results show that CagN is not delivered into host cells and instead is associated with the bacterial membrane. We demonstrate that CagN is cleaved at its C terminus by a mechanism that is independent of other cag PAI proteins. Finally, we show that a delta cagN mutant is not impaired in its ability to deliver CagA to gastric epithelial cells and initiate cell elongation.
幽门螺杆菌感染了近一半的世界人口，并与一系列胃部疾病相关。感染携带细胞毒素相关基因致病岛（cag PAI）的菌株会增加患胃癌的风险。cag PAI包含编码IV型分泌系统（T4SS）和一种传递效应蛋白CagA的基因，CagA在传递到宿主细胞后会发生酪氨酸磷酸化，并引发细胞信号传导的变化。尽管一些cag PAI基因已被证明是CagA传递所必需的，其中一部分是来自根癌土壤杆菌的T4SS基因的同源物，但大多数基因的功能或同源物尚不清楚。我们对一种这样的cag PAI蛋白CagN进行了详细研究，CagN由HP0538基因编码。我们的结果表明，CagN不会传递到宿主细胞中，而是与细菌膜相关。我们证明CagN在其C末端通过一种独立于其他cag PAI蛋白的机制被切割。最后，我们表明缺失cagN的突变体在将CagA传递到胃上皮细胞并引发细胞伸长的能力上没有受损。
