Low copper availability limits Helicobacter infection in mice.

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.