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New Publication Characterizes the Complex Methylomes of Helicobacter pylori

Monday, December 9, 2013

A new paper in Nucleic Acids Research describes the genome-wide methylation state of two strains of Helicobacter pylori, using Single Molecule, Real-Time (SMRT®) Sequencing. The paper represents the first comprehensive study of the myriad of DNA base modifications present across the genome of this major human pathogen.

The collaborative study, entitled “The complex methylome of the human gastric pathogen Helicobacter pylori” was led by the laboratory of Sebastian Suerbaum at the Institute of Medical Microbiology & Hospital Epidemiology and German Center for Infection Research, Hannover, Germany, and includes researchers from New England Biolabs, the DSMZ German Collection of Microorganisms and Cell Cultures Braunschweig, and Pacific Biosciences.

H. pylori chronically infects more than half of the world’s population and has been implicated in the formation of ulcers and gastric cancer. Its genome is known for having a “large number of restriction-modification (R-M) systems, and strain-specific diversity in R-M systems has been suggested to limit natural transformation, the major driving force of genetic diversification in H. pylori,” the authors write. They characterized strains 26695 and J99-R3, observing that the methylation patterns were significantly different between the two strains – 17 methylated sequence motifs in the former and 22 in the latter.

Among the motifs were 12 patterns associated with nine recognition sites that were not previously associated with any known methyltransferases. According to the paper, “The combined strategy of allelic disruption of candidate genes and additional functional tests led to the identification of new MTase activities in H. pylori responsible for methylation of eight of the nine novel recognition sites and, furthermore, to the description of unexpected new features of R-M systems.” Those features included “frameshift-mediated changes of sequence specificity and the interaction of one MTase with two alternative specificity subunits resulting in different methylation patterns.”

“This pathogen is not only remarkable due to its abundance of active MTases but [it] also harbors R-M systems with exceptional versatility,” Suerbaum and his collaborators report. “The data show that R-M systems are more complex than previously thought and with the further use of SMRT sequencing for the discovery and functional characterization of R-M systems, our knowledge is likely to rapidly increase.”

Suerbaum presented aspects of this research at the American Society for Microbiology conference earlier this year in a presentation entitled “Comprehensive methylome analysis of the human gastric pathogen, Helicobacter pylori.”

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