Abstract
OBJECTIVES: Increased antimicrobial resistance has necessitated innovative therapeutic strategies to combat Helicobacter pylori, a key contributor to gastric cancer (GC). Antimicrobial peptides (AMPs) derived from probiotic Lactobacillus spp. offer a promising alternative to antibiotics, with several strains demonstrating inhibitory activity against H. pylori. This study aimed to identify and characterize Lactobacillus spp.-derived AMP variants with antimicrobial properties against H. pylori to reduce the incidence of H. pylori-mediated GC. METHODS: AMPs were retrieved from various databases, followed by multistep in silico screening to identify potential candidates. The shortlisted peptides were analyzed for physicochemical and ADMET properties, and their 3D structures were predicted using PEP-FOLD4. Docking of AMPs was performed with major H. pylori virulence factors and their interacting GC host proteins using HADDOCK 2.4, and binding free energies were calculated using HawkDock. RESULTS: Of the 109 AMPs retrieved, only nine were found to have favorable biological, physicochemical, and ADMET properties. Notably, peptide seq30 exhibited potent binding to cytotoxin-associated gene A (CagA; -75.28 kcal/mol), seq55 to c-Met (-99.15 kcal/mol), seq28 to E-cadherin (-75.58 kcal/mol), and seq78 to both β-catenin (-85.52 kcal/mol) and proteinase-activated receptor 1 (-84.74 kcal/mol), indicating the ability of these AMPs to interact with major pathways involved in gastric carcinogenesis. These AMPs could serve as promising candidates for designing preventive therapeutic strategies to suppress H. pylori-induced cell invasion, which could further lead to the development of GC. CONCLUSIONS: Our findings demonstrate that AMPs seq28, seq30, seq55, and seq78 have preventive therapeutic potential against H. pylori and can be further explored for the development of therapeutic candidates to address H. pylori infection and its associated complications, such as GC.