Multiple Helicobacter pylori proteins with accessible thiol groups

Helicobacter pylori thiol-containing proteins represent a collective group of bacterial targets characterized by accessible cysteine residues that are susceptible to modification by antimicrobial agents, most notably bismuth compounds [2, 8]. These proteins include critical enzymes like urease, which allows the bacteria to survive the acidic environment of the stomach, as well as proteins involved in antioxidant defense (e.g., thioredoxin reductase) and metal homeostasis [1, 6]. Bismuth-based therapy leverages the high thiophilicity of bismuth ions to covalently bind these groups, thereby inactivating multiple essential physiological processes simultaneously [8, 11]. This multi-target approach is a key component of quadruple therapy regimens used to eradicate H. pylori infections, particularly those resistant to standard antibiotics [6, 14]. By disrupting these diverse pathways, the drugs effectively reduce bacterial colonization and promote the healing of associated gastric and duodenal ulcers [11, 13]. Because bismuth interacts with over 60 different proteins, the development of bacterial resistance to this mechanism is extremely rare [6, 8].

Other names

Helicobacter pylori thiol-containing proteinsBismuth-binding proteins of H. pyloriH. pylori cysteine-rich proteinsThiol-dependent enzymes of H. pylori

Bismuth ions (Bi3+) exhibit high thiophilicity, allowing them to covalently bind to accessible sulfhydryl (thiol) groups on various essential bacterial proteins. This binding leads to the irreversible inhibition of enzymes like urease (critical for acid survival), disruption of antioxidant systems (e.g., thioredoxin reductase), interference with iron and nickel homeostasis, and impairment of protein folding and metabolic pathways, collectively exerting a potent bactericidal effect.