Xingyu Yao1,2, Shiyu Xiao1,2, Liya Zhou1,2. 1. Department of Gastroenterology, Peking University Third Hospital, Beijing, China. 2. Beijing Key Laboratory of Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, Beijing, China.
Abstract
BACKGROUND: Bismuth-based drugs are used to treat Helicobacter pylori infection; however, the antibacterial activity of bismuth, especially against H. pylori, has not been fully elucidated. In this study, the mechanisms by which bismuth exerts its detrimental effects on H. pylori were evaluated. Methods Six H. pylori strains isolated from different patients were cultured with or without bismuth; proteins and metabolites differentially expressed in these two sets of bacteria were detected via data independent acquisition proteomic and gas chromatography-mass spectrometry metabolic approaches, respectively. Gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes database were used to identity pathway enrichment. RESULTS: 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.
BACKGROUND: Bismuth-based drugs are used to treat Helicobacter pylori infection; however, the antibacterial activity of bismuth, especially against H. pylori, has not been fully elucidated. In this study, the mechanisms by which bismuth exerts its detrimental effects on H. pylori were evaluated. Methods Six H. pylori strains isolated from different patients were cultured with or without bismuth; proteins and metabolites differentially expressed in these two sets of bacteria were detected via data independent acquisition proteomic and gas chromatography-mass spectrometry metabolic approaches, respectively. Gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes database were used to identity pathway enrichment. RESULTS: 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.
Authors: Giuseppe Losurdo; Ilaria Lacavalla; Francesco Russo; Giuseppe Riezzo; Irene Vita Brescia; Maria Rendina; Enzo Ierardi; Alfredo Di Leo Journal: Antibiotics (Basel) Date: 2022-01-10