Novel antimicrobial peptide ECCT from Chinese water snake is a potential candidate for the treatment of Helicobacter pylori infection and gastric cancer.

BACKGROUND: Helicobacter pylori (H. pylori) is a highly virulent bacterial pathogen that exhibits close association with the development of duodenal and gastric ulcers, as well as carcinomas. Several antimicrobial peptides (AMPs) have demonstrated remarkable efficacy in combating H. pylori infections. However, limited studies have been conducted on AMPs possessing anti-H. pylori activity. Herein, we report the identification and characterization of ECCT, a novel cathelicidins family AMP derived from the Chinese water snake Enhydris chinensis. MATERIALS AND METHODS: We identified a novel antimicrobial peptide, ECCT, through cDNA sequencing. The phylogeny and secondary structure of ECCT were analyzed using the neighborhood connection method. The MIC of ECCT against various pathogens was determined, and the inhibitory effect on proinflammatory cytokine transcription was detected using qPCR. Furthermore, the effects of ECCT on the MAPK inflammatory pathway induced by Helicobacter pylori were analyzed via Western Blotting. Lastly, the cytotoxic effects of ECCT on various human gastric cancer cell lines were evaluated using the MTT assay. RESULTS: ECCT exhibits potent and rapid bactericidal activity against H. pylori, with minimum inhibitory concentrations (MICs) ranging from 1.3 to 5.1 μM and complete bacterial eradication within 10 min. Additionally, ECCT demonstrates robust anti-inflammatory effects against H. pylori infection by significantly reducing the transcription and production of pro-inflammatory cytokines through inhibition of the MAPK signaling pathway. Importantly, ECCT also effectively induces apoptosis in gastric cancer cells at low concentrations and causes direct lysis at high concentrations, while maintaining low toxicity to normal cells. CONCLUSION: These findings underscore the potential of ECCT as a promising therapeutic approach for preventing and treating gastritis and gastric cancer caused by H. pylori infections. Particularly, this study highlights the multifaceted nature of ECCT as a versatile therapeutic agent, offering a novel strategy for addressing a spectrum of H. pylori-related gastric diseases.