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Characterization of the cagA-gene in Helicobacter pylori in Mongolia and detection of two EPIYA-A enriched CagA types
International Journal of Medical Microbiology ( IF 4.1 ) Pub Date : 2022-02-24 , DOI: 10.1016/j.ijmm.2022.151552
Oyunbaatar Altanbayar 1 , Avarzed Amgalanbaatar 2 , Chimeddorj Battogtokh 1 , Narmandakh Bayarjargal 3 , Dana Belick 4 , Malte Kohns Vasconcelos 4 , Colin R Mackenzie 4 , Klaus Pfeffer 4 , Birgit Henrich 4
Affiliation  

Helicobacter pylori infection is strongly associated with gastritis, gastroduodenal ulcer disease and gastric carcinoma. The virulence of H. pylori strains increases with the presence of the pathogenicity island PAI, which encodes a Type 4 Secretion System and the oncoprotein CagA. Two major CagA types can be distinguished by differences in the repetitive EPIYA region in the C-terminal sequence; the more virulent East Asian CagA type with EPIYA-A, -B, and -D motifs and the Western CagA type with EPIYA-A, -B, and C motifs, the virulence of which is associated with the multitude of EPIYA-C motifs.

In this study, the cagA gene was characterized in H. pylori strains isolated from Mongolians suffering from gastritis (80%) or ulcer (20%). The EPIYA region of 53 isolates was determined by PCR-amplification of overlapping cagA regions and subsequent Sanger sequencing. Only one H. pylori isolate carried the East Asian type (ABD) and 52 isolates the Western type of CagA, thereof 30 the EPIYA type ABC, 19 the ABCC type and one each of type ABCCCC, AAABC and AAAAB. An amino acid exchange from EPIYA-B to EPIYT-B was predominantly found in CagA proteins in strains with < 2 EPIYA-C copies (n = 25/32; p = 0.015) including the two EPIYA-A enriched CagA proteins, which have not been described to date. Due to the amino acid triplet preceding the EPIYA motif and strength of predicted phosphorylation, the multiple EPIYA-A motifs A2, A3 and A4 were shown to cluster with EPIYA-B and EPIYT-B with the unique feature of amino acid E in position − 4 to Y of EPIYA. It has been described that tyrosine-phosphorylated EPIYA-A and -B motifs counteract the EPIYA-C-driven signaling towards host cell transformation and malignancy. Thus, Mongolian H. pylori strains carrying CagA proteins not only with a few EPIYA-C segments but also with multiplied EPIYA-A segments are probably less virulent; a thesis that needs further investigation at the protein level.



中文翻译:

蒙古幽门螺杆菌cagA基因的表征和两种EPIYA-A富集的CagA类型的检测

幽门螺杆菌感染与胃炎、胃十二指肠溃疡病和胃癌密切相关。H. pylori菌株的毒力随着致病岛 PAI 的存在而增加,致病岛 PAI 编码 4 型分泌系统和癌蛋白 CagA。两种主要的 CagA 类型可以通过 C 端序列中重复 EPIYA 区域的差异来区分;具有 EPIYA-A、-B 和 -D 基序的东亚 CagA 型和具有 EPIYA-A、-B 和 C 基序的西方 CagA 型毒性更强,其毒力与大量 EPIYA-C 基序有关.

在这项研究中,cag A 基因在从患有胃炎 (80%) 或溃疡 (20%) 的蒙古人中分离出的幽门螺杆菌菌株中得到表征。53 个分离株的 EPIYA 区域通过重叠cag A 区域的 PCR 扩增和随后的 Sanger 测序确定。携带东亚型(ABD)的幽门螺杆菌仅1株,西型CagA分离株52株,其中EPIYA ABC型30株,ABCC型19株,ABCCCC、AAABC和AAAAB型各1从 EPIY A -B 到 EPIY T的氨基酸交换-B 主要存在于具有 < 2 个 EPIYA-C 拷贝 (n = 25/32; p = 0.015) 的菌株的 CagA 蛋白中,包括两种 EPIYA-A 富集的 CagA 蛋白,迄今为止尚未描述。由于 EPIYA 基序之前的氨基酸三联体和预测的磷酸化强度,显示多个 EPIYA-A 基序 A2、A3 和 A4 与 EPIYA-B 和 EPIYT-B 聚集在一起,具有氨基酸 E 在位置的独特特征 - 4 到 EPIYA 的 Y。已经描述了酪氨酸磷酸化的 EPIYA-A 和 -B 基序抵消了 EPIYA-C 驱动的针对宿主细胞转化和恶性肿瘤的信号传导。因此,蒙古H. pylori携带 CagA 蛋白的菌株不仅具有少量 EPIYA-C 片段而且还具有倍增的 EPIYA-A 片段,其毒性可能较低;需要在蛋白质水平上进一步研究的论文。

更新日期:2022-02-24
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