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

Abstract

Long-term use of proton pump inhibitors (PPIs) can increase therisk 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 thetranscriptional 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 (2mg/mL) at pH 2.0, 4.0 and 7.0 after 30 and 90minutes 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.