Division of Microbiology, Department of Biosciences, Paris-Lodron University of Salzburg, 5020 Salzburg, Austria.
Laboratory of Medical Microbiology, Hellenic Pasteur Institute, 127 Vas. Sofias Avenue, 115 21 Athens, Greece.
Toxins (Basel). 2021 Aug 24;13(9):592. doi: 10.3390/toxins13090592.
() colonizes the human stomach and can induce gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical observations suggest a role for the virulence factor cytotoxin-associated gene A (CagA) in pathogenesis. The pathogenic activity of CagA is partly regulated by tyrosine phosphorylation of C-terminal Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in host cells. However, CagA differs considerably in EPIYA motifs, whose functions have been well characterized in epithelial cells. Since CagA is fragmented in immune cells, different CagA variants may exhibit undetected functions in B cells.
B cells were infected with isolates and isogenic mutants expressing different CagA EPIYA variants. CagA translocation and tyrosine phosphorylation were investigated by Western blotting. Apoptosis was analyzed by flow cytometry and metabolic activity was detected by an MTT assay.
Isogenic CagA EPIYA variants are equally well translocated into B cells, followed by tyrosine phosphorylation and cleavage. B cell apoptosis was induced in a CagA-independent manner. However, variants containing at least one EPIYA-C motif affected metabolic activity independently of phosphorylation or multiplication of EPIYA-C motifs.
The diverse structure of CagA regulates B cell physiology, whereas B cell survival is independent of CagA.
()定植于人类胃部，可引发胃癌和黏膜相关淋巴组织 (MALT) 淋巴瘤。临床观察提示细胞毒素相关基因 A (CagA) 这一致病因子在发病机制中起作用。CagA 的致病活性部分受宿主细胞 C 端 Glu-Pro-Ile-Tyr-Ala (EPIYA) 基序酪氨酸磷酸化的调节。然而，CagA 在 EPIYA 基序上存在显著差异，其在肠上皮细胞中的功能已得到充分研究。由于 CagA 在免疫细胞中被截断，不同的 CagA 变体可能在 B 细胞中表现出未被发现的功能。
用 分离株及其表达不同 CagA EPIYA 变体的同基因突变体感染 B 细胞。通过 Western blot 检测 CagA 易位和酪氨酸磷酸化。通过流式细胞术分析细胞凋亡，通过 MTT 测定检测代谢活性。
同基因 CagA EPIYA 变体同样容易易位进入 B 细胞，随后发生酪氨酸磷酸化和切割。以 CagA 非依赖性方式诱导 B 细胞凋亡。然而，含有至少一个 EPIYA-C 基序的变体独立于磷酸化或 EPIYA-C 基序的增殖而影响代谢活性。
CagA 的多样结构调节 B 细胞生理学，而 B 细胞存活与 CagA 无关。
