The Helicobacter pylori (Hp) type IV secretion system (T4SS) forms needle-like pili, whose binding to the integrin-β₁ receptor results in injection of the CagA oncoprotein. However, the apical surface of epithelial cells is exposed to Hp, whereas integrins are basolateral receptors. Hence, the mechanism of CagA delivery into polarized gastric epithelial cells remains enigmatic. Here, we demonstrate that T4SS pilus formation during infection of polarized cells occurs predominantly at basolateral membranes, and not at apical sites. Hp accomplishes this by secreting another bacterial protein, the serine protease HtrA, which opens cell-to-cell junctions through cleaving epithelial junctional proteins including occludin, claudin-8, and E-cadherin. Using a genetic system expressing a peptide inhibitor, we demonstrate that HtrA activity is necessary for paracellular transmigration of Hp across polarized cell monolayers to reach basolateral membranes and inject CagA. The contribution of this unique signaling cascade to Hp pathogenesis is discussed.

的幽门螺杆菌（幽门螺杆菌）IV型分泌系统（T4SS）形成针状菌毛，其结合至整联-β ₁的相关蛋白的注射癌蛋白受体的结果。然而，上皮细胞的顶表面暴露于Hp，而整联蛋白是基底外侧受体。因此，CagA传递到极化胃上皮细胞中的机制仍然是一个谜。在这里，我们证明了在极化细胞感染过程中T4SS菌毛的形成主要发生在基底外侧膜上，而不是在根尖处。生命值通过分泌另一种细菌蛋白丝氨酸蛋白酶HtrA来实现此目的，该蛋白通过切割上皮连接蛋白（包括occludin，claudin-8和E-cadherin）来打开细胞间连接。使用表达肽抑制剂的遗传系统，我们证明HtrA活性是Hp跨极化细胞单层跨细胞转运到基底外侧膜并注射CagA所必需的。讨论了这种独特的信号级联对Hp发病机制的贡献。