Low copper availability limits Helicobacter infection in mice. (8th January 2020)

• Record Type: Journal Article
• Authors: Esposito, Roberta; Vllahu, Megi; Morello, Silvana; Baldantoni, Daniela; Bellino, Alessandro; Petrella, Antonello; Eletto, Daniela; Porta, Amalia; Tosco, Alessandra
• Is Part Of: FEBS journal. Volume 287:Number 14(2020)
• Page Start: 2948
• Page End: 2960
• Publication Date: 2020-01-08
• Subjects: copper -- Helicobacter infection -- inflammation -- tetrathiomolybdate -- TFF1; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15188
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Copper is an essential element for all living organisms; however, it becomes toxic at high concentrations due to its ability to participate in many redox reactions. This vital micronutrient balance plays an important role in the battle between host and pathogen, due to its use by the host to intoxicate pathogens. In this study, we explore the effects of copper deprivation on Helicobacter infection in mice using the copper chelator tetrathiomolybdate. Our results reveal that Helicobacter infection significantly reduces copper concentration in mice stomachs without affecting its circulating levels. Moreover, in copper‐deprived mice, bacteria hardly colonize the epithelium and mice show less gastric damage in comparison with the infected ones. However, when the copper chelator is administered after infection, the condition of the mouse stomachs declines. This could be explained by the lower copper availability in tetrathiomolybdate‐treated mice, which would reduce macrophages' action against the pathogen. In this scenario, we observe that the protective factor trefoil factor 1 is induced upon copper‐deprived conditions, probably contributing to the inefficacy of infection, whereas, when the chelator is administered after infection, the gene is already silenced by bacteria and cannot be restored. In conclusion, our data suggest that Helicobacter takes advantage of gastric copper reducing its availability for the host and that copper levels have an impact on the outcome of infection. Abstract : Our data suggest that Helicobacter utilizes gastric copper for the efficacy of infection by reducing its availability for the host. In copper‐deprived animals, bacteria are unable to locate a comfortable environment and hardly colonize the epithelium. In this condition, mice stomachs are partially damaged in comparison with the infected ones; moreover, pro‐inflammatory chemokines are reduced, potentially as a consequence of higher levels of trefoil factor 1.