Metal-binding proteins and metal metabolism in Helicobacter pylori

Metal metabolism in Helicobacter pylori encompasses a complex network of proteins dedicated to the acquisition, trafficking, and regulation of essential transition metals, most notably nickel and iron (Microbiology and Molecular Biology Reviews, 2011). Nickel is a critical cofactor for urease, an enzyme that allows H. pylori to neutralize stomach acid by producing ammonia, and for [NiFe]-hydrogenase, which is involved in energy metabolism (Metallomics, 2015). The system includes transporters like NixA, storage proteins such as Hpn and Hpn-like, and global regulators like the nickel-responsive NikR and the ferric uptake regulator (Fur) (Journal of Inorganic Biochemistry, 2018). Because these metals are vital for survival and pathogenesis, the metal-binding sites of these proteins are significant therapeutic targets. Bismuth-based drugs, a cornerstone of H. pylori eradication therapy, function by displacing essential metals from these proteins or binding to key thiol groups, effectively inactivating enzymes like urease and disrupting the pathogen's homeostasis (Metallomics, 2012). This multi-protein system is essential for the infection's persistence and its role in gastric ulcers and adenocarcinoma (Frontiers in Microbiology, 2019).

Other names

Helicobacter pylori metal homeostasis systemH. pylori metallomeNickel and iron metabolism in H. pyloriUrease-associated metal metabolism

Bismuth compounds inhibit H. pylori by competing with or displacing essential metal ions (primarily nickel and iron) from binding sites in proteins such as urease and NikR, or by binding to functional thiol groups, leading to enzyme inactivation and disruption of metal homeostasis (Journal of Biological Inorganic Chemistry, 2014).