Genetic variants of Helicobacter pylori type IV secretion system components CagL and CagI and their association with clinical outcomes.
Genetic variants of Helicobacter pylori type IV secretion system components CagL and CagI and their association with clinical outcomes.
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DOI：
10.1186/s13099-017-0165-1
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发表时间：
2017
期刊：
影响因子：
4.2
通讯作者：
Azuma T
中科院分区：
文献类型：
--
作者：
Ogawa H;Iwamoto A;Tanahashi T;Okada R;Yamamoto K;Nishiumi S;Yoshida M;Azuma T
幽门螺杆菌感染与慢性胃炎（CG）、胃溃疡（GU）、十二指肠溃疡（DU）和胃癌（GC）的风险相关。幽门螺杆菌Cag IV型分泌系统（TFSS）将毒力因子细胞毒素相关基因A蛋白易位到宿主细胞中，并在引发胃癌的过程中发挥重要作用。 CagL 和 CagI 蛋白是 TFSS 的组成部分。 CagL 的 Arg-Gly-Asp (RGD) 基序以及 CagL 和 CagI 的 6 个最远端 C 末端氨基酸（Ser-Lys-Ile-Ile-Val-Lys 和 Ser-Lys-Val-Ile-Val-Lys）对于 TFSS 粘附到宿主细胞至关重要。此外，CagL 变体 Tyr58Glu59 先前已被证明与 GC 患者相关。我们从东南亚的 17 名 CG、8 名 GU、8 名 DU 和 10 名 GC 患者中分离出 43 株幽门螺杆菌。提取总 DNA 并使用 MiSeq 进行测序。从 CG 患者中分离出的幽门螺杆菌菌株 ATCC 26695 用作参考。我们使用全基因组测序 (WGS) 检查了幽门螺杆菌 cagL 和 cagI 的完整序列，并分析了单核苷酸变异和氨基酸变化 (AAC) 是否与不良临床结果相关。由于 cagPAI 重排，三个分离株被排除在分析之外。 CagL RGD 基序在 39 个分离株 (97.5%) 中是保守的。 C 末端基序中的 CagL-Glu59 和 Ile234 在 GC 患者的 10 份幽门螺杆菌分离株中更为常见（分别为 p < 0.001 和 p < 0.05）。当排除来自 GC 患者的 5 个越南分离株时，CagL-Glu59 仍然显着（p < 0.05），但 Ile234 则不然。仅在一种分离株中发现了 CagL-Tyr58。 CagI C 末端基序在所有 40 个分离株中完全保守，并且 CagI 中没有显着的 AAC。使用全基因组测序，我们分析了临床幽门螺杆菌分离株中的遗传变异，并鉴定了未表征的 CagL 和 CagI 序列中与胃癌发生相关的假定的新变异和候选变异。特别是，CagL-Glu59 可能与 GC 相关。本文的在线版本 (doi:10.1186/s13099-017-0165-1) 包含补充材料，可供授权用户使用。
Helicobacter pylori infection is associated with risk for chronic gastritis (CG), gastric ulcer (GU), duodenal ulcer (DU), and gastric cancer (GC). The H. pylori Cag type IV secretion system (TFSS) translocates the virulence factor cytotoxin-associated gene A protein into host cells and plays an important role in initiating gastric carcinogenesis. The CagL and CagI proteins are components of the TFSS. The Arg-Gly-Asp (RGD) motif of CagL, and the six most distal C-terminal amino acids (Ser-Lys-Ile-Ile-Val-Lys, and Ser-Lys-Val-Ile-Val-Lys) of CagL and CagI are essential for TFSS adhesion to host cells. Additionally, the CagL variant Tyr58Glu59 was previously shown to be associated with GC patients. We isolated 43 H. pylori isolates from 17 CG, 8 GU, 8 DU, and 10 GC patients in Southeast Asia. Total DNAs were extracted and sequenced with MiSeq. H. pylori strain ATCC 26695, which was isolated from CG patients, was used as a reference. We examined the full sequences of H. pylori cagL and cagI using whole-genome sequencing (WGS), and analyzed whether single nucleotide variants and amino acid changes (AACs) correlated with adverse clinical outcomes. Three isolates were excluded from the analysis due to cagPAI rearrangements. CagL RGD motifs were conserved in 39 isolates (97.5%). CagL-Glu59 and Ile234 in the C-terminal motif were more common in 10 H. pylori isolates from GC patients (p < 0.001 and p < 0.05, respectively). When 5 Vietnamese isolates from GC patients were excluded, CagL-Glu59 still remains significant (p < 0.05), but not Ile234. CagL-Tyr58 was seen in only one isolate. The CagI C-terminal motif was completely conserved across all 40 isolates, and there were no significant AACs in CagI. Using WGS, we analyzed genetic variants in clinical H. pylori isolates and identified putative novel and candidate variants in uncharacterized CagL and CagI sequences that are related to gastric carcinogenesis. In particular, CagL-Glu59 has the possible association with GC. The online version of this article (doi:10.1186/s13099-017-0165-1) contains supplementary material, which is available to authorized users.