研究动态
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在不同pH值和质子泵抑制剂暴露条件下,对幽门螺杆菌细菌毒性相关基因-致病性岛的转录分析。

Transcriptional analysis of Helicobacter pylori cytotoxic-associated gene-pathogenicity island in response to different pH levels and proton pump inhibitor exposure.

发表日期:2023 Sep 04
作者: Fatemeh Rezaei, Masoud Alebouyeh, Seyedeh Zohre Mirbagheri, Amir Ebrahimi, Abbas Rahimi Foroushani, Ronak Bakhtiari
来源: GENES & DEVELOPMENT

摘要:

长期使用质子泵抑制剂(PPIs)可以增加幽门螺杆菌感染患者胃癌的风险,然而对于它们对幽门螺杆菌致病性的影响尚无数据。本研究旨在研究不同pH值下奥美拉唑对临床幽门螺杆菌分离株基因转录的影响,这些基因是与细胞毒素相关基因-致病性岛(cag-PAI)的关键调节因子。因此,从患者的胃活检样本中选择具有相同毒力基因型的幽门螺杆菌分离株,研究在omeprazole(2 mg/mL)存在或不存在的情况下,在pH 2.0、4.0和7.0条件下进行30分钟和90分钟的处理后,cag-PAI基因的转录修饰。每次实验分别记录基因的相对转录水平变化。在18个幽门螺杆菌分离株中,有4个菌株检测到cag-PAI空位,而77.7%、83.3%和83.3%的cag-PAI阳性菌株被鉴定为cagA、cagL和cagY的存在。对选择的菌株进行的转录分析显示,在pH 2.0和4.0条件下,在处理30分钟和90分钟后,cagA和cagL的表达上调。在基因诱导的程度和时间上,菌株之间的表达水平存在多样性。我们的结果显示,奥美拉唑可以在酸性pH下增加幽门螺杆菌cagA和cagL的表达。菌株之间的异质性可能会对它们与PPIs的相互作用程度产生影响。进一步的研究需要确立这种相关性。© 2023. Indian Society of Gastroenterology.
Long-term use of proton pump inhibitors (PPIs) can increase the risk of gastric cancer in Helicobacter pylori-infected patients; nevertheless, there is no data about their impact on the pathogenicity of H. pylori. This study aimed at investigating the transcriptional alteration of key gene mediators of cytotoxin-associated gene-pathogenicity island (cag-PAI) among clinical H. pylori isolates in response to omeprazole at different pH levels.Accordingly, H. pylori isolates with the same virulence genotypes selected from the gastric biopsies of patients and transcriptional alteration in the cag-PAI genes studied in the presence or absence of omeprazole (2 mg/mL) at pH 2.0, 4.0 and 7.0 after 30 and 90 minutes of the treatment. Relative changes in the transcriptional levels were recorded in each assay, separately.Of 18 H. pylori isolates, the cag-PAI empty site was detected in four strains, while the presence of cagA, cagL and cagY was characterized in 77.7%, 83.3% and 83.3% of the cag-PAI-positive strains, respectively. Transcriptional analysis of the selected strains showed up-regulation of cagA and cagL, mainly at pH 2.0 and 4.0 after 30 and 90-minute exposure. A diversity in the expression levels of cag-PAI genes was seen among the strains at the extent and time of induction.Our results showed that omeprazole could increase the expression of H. pylori cagA and cagL at acidic pH. Heterogeneity among the strains probably has an impact on the extent of their interplay with PPIs. Further studies are needed to establish this correlation.© 2023. Indian Society of Gastroenterology.