Helicobacter pylori CagA inhibits endocytosis of cytotoxin VacA in host cells
Helicobacter pylori CagA inhibits endocytosis of cytotoxin VacA in host cells
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DOI：
10.1242/dmm.004879
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发表时间：
2010-09-01
影响因子：
4.3
通讯作者：
Nakamura, Kazuyuki
中科院分区：
文献类型：
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作者：
Akada, Junko K.;Aoki, Hiroki;Nakamura, Kazuyuki
幽门螺杆菌是一种导致慢性胃炎和癌症的常见病原体，它已经进化到在人类胃中建立持续感染。流行病学证据表明，同时具有高活性空泡细胞毒素A（VacA）和细胞毒素相关基因A（CagA）这两种主要毒力因子的幽门螺杆菌在适应宿主环境方面具有优势。然而，VacA 和 CagA 之间的机制关系仍然不清楚。在这里，我们报告了 CagA 干扰真核细胞的内吞作用，正如酵母全基因组筛选所揭示的那样。此外，CagA 抑制胃上皮细胞中的胞饮内吞作用和 VacA 的细胞毒性，而不影响网格蛋白依赖性内吞作用。我们的数据表明，幽门螺杆菌分泌VacA攻击远处的宿主细胞，同时将CagA注射到细菌直接附着的胃上皮细胞中，从而保护这些附着的宿主细胞免受VacA的细胞毒性，并创建局部生态位。这种机制可能允许幽门螺杆菌平衡对一组宿主细胞的损害与另一组宿主细胞的保存，从而实现持续感染。
Helicobacter pylori, a common pathogen that causes chronic gastritis and cancer, has evolved to establish persistent infections in the human stomach. Epidemiological evidence suggests that H. pylori with both highly active vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), the major virulence factors, has an advantage in adapting to the host environment. However, the mechanistic relationship between VacA and CagA remains obscure. Here, we report that CagA interferes with eukaryotic endocytosis, as revealed by genome-wide screening in yeast. Moreover, CagA suppresses pinocytic endocytosis and the cytotoxicity of VacA in gastric epithelial cells without affecting clathrin-dependent endocytosis. Our data suggest that H. pylori secretes VacA to attack distant host cells while injecting CagA into the gastric epithelial cells to which the bacteria are directly attached, thereby protecting these attached host cells from the cytotoxicity of VacA and creating a local ecological niche. This mechanism might allow H. pylori to balance damage to one population of host cells with the preservation of another, allowing for persistent infection.