Pathogenesis of Helicobacter Pylori (HP) vacuolating toxin A (vacA) depends on polymorphic diversity within the signal (s), middle (m), intermediate (i), deletion (d) and c-regions. These regions show distinct allelic diversity. The s-region, m-region and the c-region (a 15 bp deletion at the 3′-end region of the p55 domain of the vacA gene) exist as 2 types (s1, s2, m1, m2, c1 and c2), while the i–region has 3 allelic types (i1, i2 and i3). The locus of d-region of the vacA gene has also been classified into 2 genotypes, namely d1 and d2. We investigated the “d-region”/“loop region” through bioinformatics, to predict its properties and relation to disease. One thousand two hundred fifty-nine strains from the NCBI nucleotide database and the dryad database with complete vacA sequences were included in the study. The sequences were aligned using BioEdit and analyzed using Lasergene and BLAST. The secondary structure and physicochemical properties of the region were predicted using PredictProtein. We identified 31 highly polymorphic genotypes in the “d-region”, with a mean length of 34 amino acids (9 ~ 55 amino acids). We further classified the 31 genotypes into 3 main types, namely K-type (strains starting with the KDKP motif in the “d-region”), Q-type (strains starting with the KNQT motif), and E-type (strains starting with the ESKT motif) respectively. The most common type, K-type, is more prevalent in cancer patients (80.87%) and is associated with the s1i1m1c1 genotypes (P < .01). Incidentally, a new region expressing sequence diversity (2 aa deletion) at the C-terminus of the p55 domain of vacA was identified during bioinformatics analysis. Prediction of secondary structures shows that the “d-region” adopts a loop conformation and is a disordered region.

中文翻译：

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从全球菌株中鉴定出幽门螺杆菌 VacA d 区的新基因型

幽门螺杆菌 (HP) 空泡毒素 A (vacA) 的发病机制取决于信号 (s)、中间 (m)、中间 (i)、缺失 (d) 和 c 区域内的多态性。这些区域显示出明显的等位基因多样性。s 区、m 区和 c 区（vacA 基因 p55 结构域 3' 端区域的 15 bp 缺失）存在 2 种类型（s1、s2、m1、m2、c1 和 c2 )，而 i 区域有 3 种等位基因类型（i1、i2 和 i3）。vacA基因d区的位点也分为2个基因型，即d1和d2。我们通过生物信息学研究了“d-region”/“loop region”，以预测其特性和与疾病的关系。该研究包括来自 NCBI 核苷酸数据库和树妖数据库的 1259 株具有完整 vacA 序列的菌株。使用 BioEdit 比对序列并使用 Lasergene 和 BLAST 进行分析。使用 PredictProtein 预测该区域的二级结构和理化性质。我们在“d区”鉴定了31个高度多态性基因型，平均长度为34个氨基酸（9~55个氨基酸）。我们进一步将 31 种基因型分为 3 种主要类型，即 K 型（以“d 区”中的 KDKP 基序开头的菌株）、Q 型（以 KNQT 基序开头的菌株）和 E 型（以与 ESKT 主题）分别。最常见的类型 K 型在癌症患者中更为普遍 (80.87%)，并且与 s1i1m1c1 基因型相关 (P < .01)。顺便提一下，在生物信息学分析期间，在 vacA 的 p55 结构域的 C 端发现了一个表达序列多样性（2 个氨基酸缺失）的新区域。