1887

Abstract

Proton pump inhibitors (PPIs) are associated with the development of infection in humans. Though it is assumed that PPIs mediate this effect through gastric acid suppression, there has been little investigation into whether PPIs, or ambient pH, might directly affect the expression of toxin genes. In the present study, ribotypes 001, 027 and 078 obtained from human subjects were grown under anaerobic conditions prepared at pHs of 5, 7.3 and 9. Matched trios were exposed to 100 µM and 200 µM of omeprazole along with PPI untreated controls. Custom designed reverse transcription quantitative PCR hydrolysis probes were used to assess gene expression for toxins A (), B () and binary toxin (), as well as their positive regulators ( and ), using , which encodes 16S rRNA, as a constitutively expressed reference gene. and , negative regulators of toxin expression, were also assessed. Basic pH resulted in greater expression of , and with PPI exposure a 120-fold higher expression was noted with ribotype 001. and expressions were much less responsive to pH or PPIs, though a clear response to acidic pH and PPI exposure was observed in ribotype 027. and expressions were largely unaffected, except with ribotype 027; low pH and PPIs resulted in their greater expression, though to a lesser degree than with toxin genes and their positive regulators. Non-neutral pH and PPI exposure appear to have an effect on , one that has a net effect towards toxin gene expression.

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2013-10-01
2019-12-12
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