Bismuth-binding bacterial proteins and thiol-containing biomolecules

This target group comprises a diverse array of proteins and small molecules, primarily within Helicobacter pylori, that exhibit a high affinity for bismuth ions. The most prominent bacterial target is the enzyme urease, which is critical for H. pylori survival in the acidic gastric environment as it catalyzes the hydrolysis of urea into ammonia to neutralize stomach acid [1]. Bismuth also targets other essential bacterial enzymes, including alcohol dehydrogenase, fumarate reductase, and various phospholipases, by binding to their cysteine-rich thiol groups [2]. Beyond enzymes, bismuth interacts with thiol-containing biomolecules such as glutathione and metallothionein, disrupting the redox balance and structural integrity of the bacterial cell [3]. Clinically, these interactions are exploited using bismuth-based compounds to treat H. pylori infections and associated peptic ulcers, typically as a component of bismuth-containing quadruple therapy (BCQT) [4]. The multi-target nature of bismuth makes it difficult for bacteria to develop resistance compared to single-target antibiotics [5]. [1] https://pubmed.ncbi.nlm.nih.gov/11034301/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436061/ [3] https://pubchem.ncbi.nlm.nih.gov/compound/Bismuth-subsalicylate#section=Mechanism-of-Action [4] https://www.statpearls.com/ArticleLibrary/viewarticle/18343 [5] https://www.nature.com/articles/s41467-018-07699-x

Other names

Bismuth targetsHelicobacter pylori urease and thiol-rich proteinsBacterial sulfhydryl-containing enzymesBismuth-sensitive bacterial biomolecules

Bismuth ions bind with high affinity to the sulfhydryl (thiol) groups of bacterial enzymes and biomolecules, leading to the inhibition of essential metabolic pathways, disruption of the cell wall, and induction of oxidative stress.