Unraveling the plasmidome of Helicobacter pylori: an unexplored source of potential pathogenicity

2.Helicobacter pylori is a significant human pathogen associated with gastric diseases, yet the role of plasmids in its pathogenicity remains underexplored. This study provides a comprehensive genomic and functional characterization of the H. pylori plasmidome using publicly available plasmid sequences. Of 335 plasmids analyzed, 127 non-redundant representatives were selected for downstream analysis. MobMess network and Mash distance-based analyses suggest two major plasmid groups (G1 and G2) with distinct genomic and functional profiles. G1 plasmids were enriched in genes related to the Fic protein family and ABC transporters, potentially contributing to pathogenicity through post-translational modification and antibiotic extrusion, respectively. In contrast, G2 plasmids were predominantly associated with the Type IV Secretion System (T4SS) and conjugative elements, indicating a role in horizontal gene transfer. Notably, compound genes were linked to pathogenic proteins, including ClpP, VapD, and a putative vacuolating cytotoxin-related gene. This study underscores the functional diversity of the H. pylori plasmidome and highlights the need for experimental validation to clarify its role in pathogenicity, antimicrobial resistance, and adaptability. 3. Impact statementAlthough Helicobacter pylori is well-studied as the primary etiologic agent of gastric diseases, information about the role of plasmids in this species remains limited. This study contributes to microbial genomics by characterizing the genomic and functional diversity of the H. pylori plasmidome available in public databases. Our findings highlight the importance of monitoring and conducting experimental assays to better understand the role of plasmids in pathogenic bacteria like H. pylori, which may harbor genes related to pathogenicity and antimicrobial resistance. 4. Data summaryThe authors confirm all supporting data, and protocols have been provided within the article or through supplementary data files. The code employed for bioinformatic analyses can be obtained from the corresponding author upon request.