title: The Complete Genome Sequence of the Murine Pathobiont Helicobacter typhlonius.
abstract: BACKGROUND
  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 MIT 97-6810, obtained through single-molecule real-time sequencing.
  
  
  RESULTS
  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 RNA genes were identified. Numerous pathogenic features were found, including a putative pathogenicity island (PAIs) containing components of type IV secretion system, virulence-associated proteins and cag PAI protein. We compared the genome of H. typhlonius to those of the murine pathobiont H. hepaticus and human pathobiont H. 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 eight distinct recognition motifs for adenine and cytosine methylation. H. typhlonius shares four of its recognition motifs with H. pylori.
  
  
  CONCLUSIONS
  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 future 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.
authors.affiliation: Leiden Genome Technology Center, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Frank
authors.affiliation: Department of Human Genetics, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Celia
authors.initials: C
authors.lastname: Dingemanse
authors.affiliation: Leiden Genome Technology Center, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Arnoud M
authors.initials: AM
authors.lastname: Schmitz
authors.affiliation: Leiden Genome Technology Center, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Rolf H A M
authors.initials: RH
authors.lastname: Vossen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Gert-Jan B
authors.initials: GJ
authors.lastname: van Ommen
authors.affiliation: Leiden Genome Technology Center, Leiden University Medical CenterLeiden, Netherlands; Department of Human Genetics, Leiden University Medical CenterLeiden, Netherlands; Department of Clinical Genetics, Leiden University Medical CenterLeiden, Netherlands.
authors.forename: Johan T
authors.initials: JT
authors.lastname: den Dunnen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Els C
authors.initials: EC
authors.lastname: Robanus-Maandag
authors.affiliation: Leiden Genome Technology Center, Leiden University Medical CenterLeiden, Netherlands; Department of Human Genetics, Leiden University Medical CenterLeiden, Netherlands.
authors.forename: Seyed Yahya
authors.initials: SY
authors.lastname: Anvar
keywords: Helicobacter typhlonius; Pacific Biosciences; genome assembly; methylation; pathogenicity; single-molecule real-time sequencing