Integrative proteomic and metabolomic analyses reveal the mechanism by which bismuth enables Helicobacter pylori eradication.

Bismuth inhibited H. pylori growth in vitro via the following mechanisms: downregulation of virulence proteins CagA and VacA; disruption of flagella assembly responsible for bacterial colonization; and inhibition of antioxidant enzymes, including catalase, catalase-related peroxidase, and superoxide dismutase. Diverse metabolic pathways related to growth and RNA translation in H. pylori were disrupted by bismuth. Bismuth treatment impaired many biological processes in H. pylori, including antioxidant response and purine, pyrimidine, amino acid, and carbon metabolism. Conclusions The findings of this study suggest that motility, virulence factors CagA and VacA, antioxidant defense system, and many important metabolic pathways associated with bacterial growth, including nucleotide and amino acid metabolism and translation in H. pylori, are inhibited by bismuth. This study provides novel insights into the mechanism by which bismuth eradicates H. pylori upon being incorporated into quadruple therapy.