In this study, we reveal the complete sequence of the Helicobacter typhlonius genome along with its annotation and global methylation state at single-nucleotide resolution.. The complete genome sequence of Helicobacter typhlonius

Immuno-compromised mice infected with Helicobacter typhlonius are used to model microbially inducted inflammatory bowel disease (IBD). The specific mechanism through which H. typhlonius induces and promotes IBD is not fully understood. Access to the genome sequence is essential to examine emergent properties of this organism, such as its pathogenicity. To this end, we present the complete genome sequence of H. typhlonius, obtained through single-molecule real-time sequencing. The genome was assembled into a single circularized contig measuring 1.92 Mbp with an average GC content of 38.8%. In total 2,117 protein-encoding genes and 43 RNAs were identified. Numerous pathogenic features were found, including a putative pathogenicity island containing components of type IV secretion system, virulence-associated proteins and cag pathogenicity island protein. We compared the genome of H. typhlonius to those of the murine pathobiont Helicobacter hepaticus and human pathobiont Helicobacter pylori. H. typhlonius resembles H. hepaticus most with 1,594 (75.3%) of its genes being orthologous to genes in H. hepaticus. Determination of the global methylation state revealed seven distinct recognition motifs for adenine methylation. H. typhlonius shares four of its recognition motifs with H. pylori. The three remaining motifs are present in H. typhlonius exclusively. The complete genome sequence of H. typhlonius MIT 97-6810 enabled us to identify many pathogenic features suggesting that H. typhlonius can act as a pathogen. Follow-up studies are necessary to evaluate the true nature of its pathogenic capabilities. We found many methylated sites and a plethora of restriction-modification systems. The genome, together with the methylome, will provide an essential resource for forthcoming studies investigating gene regulation, host interaction and pathogenicity of H. typhlonius. In turn, this work can contribute to unraveling the role of Helicobacter in enteric disease.