Chronic in vivo exposure to Helicobacter pylori VacA: Assessing the efficacy of automated and long-term intragastric toxin infusion

<jats:title>Abstract</jats:title><jats:p><jats:italic>Helicobacter pylori</jats:italic> (<jats:italic>Hp</jats:italic>) secrete VacA, a diffusible pore-forming exotoxin that is epidemiologically linked to gastric disease in humans. <jats:italic>In vitro</jats:italic> studies indicate that VacA modulates gastric epithelial and immune cells, but the <jats:italic>in vivo</jats:italic> contributions of VacA as an important determinant of <jats:italic>Hp</jats:italic> colonization and chronic infection remain poorly understood. To identify perturbations in the stomachs of C57BL/6 or BALB/C mice that result specifically from extended VacA exposure, we evaluated the efficacy of administering purified toxin using automated infusion via surgically-implanted, intragastric catheters. At 3 and 30 days of interrupted infusion, VacA was detected in association with gastric glands. In contrast to previously-reported tissue damage resulting from short term exposure to <jats:italic>Hp</jats:italic> extracts administered by oral gavage, extended infusion of VacA did not damage stomach, esophageal, intestinal, or liver tissue. However, several alterations previously reported during <jats:italic>Hp</jats:italic> infection were detected in animals infused with VacA, including reduction of the gastric mucus layer, and increased vacuolation of parietal cells. VacA infusion invoked an immune response, as indicated by the detection of circulating VacA antibodies. These foundational studies support the use of VacA infusion for identifying gastric alterations that are unambiguously attributable to long-term exposure to toxin.</jats:p>