Posttranslational modifications in Helicobacter pylori-associated gastric pathogenesis: Bridging inflammation and carcinogenesis

Abstract

Helicobacter pylori (H. pylori), a Group I carcinogen that affects approximately half of the global population, is the primary aetiological agent of chronic gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Its pathogenesis involves intricate interactions among bacterial virulence factors, host genetics, and environmental factors. We detail the critical role of diverse protein posttranslational modifications (PTMs) in mediating H. pylori-induced gastric mucosal damage and carcinogenesis. We describe how H. pylori exploits and dysregulates a broad spectrum of host and bacterial PTMs (encompassing acetylation, ubiquitination, S-nitrosylation, disulfide bond formation, citrullination, methylation, glycosylation, phosphorylation, SUMOylation, and ADP-ribosylation) to establish infection, evade immune responses, drive chronic inflammation, and promote malignant transformation. Collectively, these findings reveal a complex, multilayered PTM network that is central to H. pylori pathogenesis. Understanding these mechanisms provides crucial insights for the development of novel diagnostic biomarkers; methylation profiles; anti-citrullinate keratin 1 (Cit-K1) antibodies, maps of PTM dynamics; targeted therapeutic strategies, including PTM enzyme inhibitors, antivirulence agents such as H. pylori disulfide bond-forming protein A inhibitors, epigenetic modulators, glycoconjugate vaccines/adhesion blockers, and optimized drug delivery systems such as N-acetylcysteine liposomes. Furthermore, this knowledge supports improved risk stratification for managing persistent cancer risk even after eradication.