Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Infect Genet Evol. 2018 Jun;60:26-34. doi: 10.1016/j.meegid.2018.02.017. Epub 2018 Feb 13.
Helicobacter pylori (H. pylori) is one of the most genetically diverse bacterial pathogens that persistently colonizes the human gastric epithelium. This remarkable genomic plasticity may act as a driving force for successful adaptation and persistence of the bacteria in the harsh gastric environment. Outer inflammatory protein A (OipA) encoded by oipA gene (HP0638/hopH) is a member of the outer membrane proteins (OMPs) of H. pylori involved in induction of IL-8 secretion and is associated with development of peptic ulcer and gastric cancer. Expression of OipA is regulated by phase variation within a CT dinucleotide repeat motif of the oipA gene. In this study we carried out direct DNA sequence analysis of 53 amplified fragments to investigate the oipA "On/Off" status among Iranian H. pylori isolates from patients with various gastric diseases. The prevalence of cagL, cagA, EPIYA motifs, vacA alleles, babA2 and sabA genotypes as well as cagPAI integrity of the isolates were determined by PCR. Our results demonstrated a high prevalence of strains with functional oipA status (79%) and significant associations were found between functional oipA and cagA (P = 0.027) and vacA s1m1 (P = 0.022) genotypes. The vacA s1m2 genotype was also found to be statistically associated with PUD (P = 0.0001). Interestingly, we showed that H. pylori strains with intact cagPAI co-expressed oipA gene in a significant synergistic relationship (P < 0.01). However, no significant association was observed between the functional oipA status and clinical outcomes (P > 0.05). In conclusion, our findings denotes great diversity in the number and pattern of CT dinucleotide repeats of oipA among Iranian H. pylori strains. The synergistic link between functional oipA and other important virulence factors is proposed to be critical in the pathogenesis of H. pylori, which needs further studies with a larger number of samples.
幽门螺杆菌（H. pylori）是一种遗传多样性最高的细菌病原体，其持续定植于人类胃上皮细胞。这种显著的基因组可塑性可能是细菌在恶劣的胃环境中成功适应和生存的驱动力。由 oipA 基因（HP0638/hopH）编码的外膜炎症蛋白 A（OipA）是幽门螺杆菌外膜蛋白（OMPs）的成员，参与诱导 IL-8 分泌，与消化性溃疡和胃癌的发展有关。OipA 的表达受 oipA 基因中 CT 二核苷酸重复基序的相位变化调节。在这项研究中，我们对 53 个扩增片段进行了直接 DNA 序列分析，以研究伊朗不同胃部疾病患者的幽门螺杆菌分离株中 oipA 的“开/关”状态。通过 PCR 确定了 cagL、cagA、EPIYA 基序、vacA 等位基因、babA2 和 sabA 基因型以及 cagPAI 完整性的存在情况。我们的结果表明，具有功能性 oipA 状态的菌株患病率很高（79%），并且在功能性 oipA 与 cagA（P=0.027）和 vacA s1m1（P=0.022）基因型之间存在显著相关性。vacA s1m2 基因型也与 PUD（P=0.0001）存在统计学关联。有趣的是，我们表明具有完整 cagPAI 的幽门螺杆菌菌株以显著协同关系共表达 oipA 基因（P<0.01）。然而，在功能性 oipA 状态与临床结果之间未观察到显著相关性（P>0.05）。总之，我们的研究结果表明，伊朗幽门螺杆菌菌株中 oipA 的 CT 二核苷酸重复数量和模式存在很大的多样性。功能性 oipA 与其他重要毒力因子之间的协同关系被认为在幽门螺杆菌的发病机制中至关重要，这需要进一步的研究和更多的样本。
