Functional and computational characterization of methyltransferases of Helicobacter pylori

Gottschall, Wilhelm (2026): Functional and computational characterization of methyltransferases of Helicobacter pylori. Dissertation, LMU München: Medizinische Fakultät

Abstract

Helicobacter pylori is unique among bacteria because it is known to have one of the larg- est numbers of restriction-modification (RM) systems in its genome. To better understand how RM systems contribute to H. pylori’s evolution, we analyzed 541 H. pylori genomes representing the seven major phylogeographic populations of this pathogen, and demon- strated that type II RM systems are the most conserved in this species. We also showed that type II sequence motifs face different levels of natural selection. Positive as well as negative correlations could be observed between the presence of certain type II methyl- transferases (MTases) and their cognate target motifs undergoing methylation. These re- sults suggest there to be an evolutionary relationship between RM systems and their cor- responding target sequences. Additionally, we investigated the evolution of the ACGT motif recognized by the M.Hpy99XI MTase. Our analysis showed that this motif is the result of expansions and contractions due to mutations and deamination events driven by environmental conditions specific to certain locations. MTases have been implicated in influencing the transcriptome through gene regulation. To further characterize the role of MTases in transcription, we decided to study the strictly orphan (i.e., always lacking a matching endonuclease) MTase M.Hpy99XIX since it can- not fulfill the classical function in phage defense. The removal of the M.Hpy99XIX MTase in H. pylori, resulting in a loss of ATTAAT methylation, has been shown to have a significant influence on gene expression and phenotype. Mutation of a single ATTAAT motif in the promoter region of the iron-acquisition gene frpB1 resulted in a variety of effects on phenotype and the expression of some genes related to iron metabolism. Our research suggests that M.Hpy99XIX regulates gene expression via a two-step model. Firstly, we demonstrate that genes are directly regulated by the methylation of ATTAAT motifs located in the promoter region. Secondly, metabolic pathways are affected by the indirect, downstream consequences of deregulating genes that are directly controlled by ATTAAT methylation. The ferric uptake regulator (Fur) has been reported to regulate iron homeostasis, and we propose that M.Hpy99XIX is also involved in this regulation.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Helicobacter pylori, methyltransferase, transcriptomic regulation
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 2. März 2026
• 1. Bericht­erstatter:in: Suerbaum, Sebastian