Date Thesis Awarded
Honors Thesis -- Open Access
Bachelors of Science (BS)
Mark H. Forsyth
Helicobacter pylori is a gram-negative spiral-shaped bacterium that colonizes the gastric epithelium and is the leading cause of gastric adenocarcinoma globally. For both H. pylori and many other bacterial species, there is an increasing body of evidence that methylation by restriction-modification systems regulates gene expression in addition to its traditional role in genome protection. The study aimed to further elucidate the mechanisms through which H. pylori achieves methylome plasticity. We demonstrated that the Type I DNA methyltransferase hsdM1 (HP0463) is regulated by the main acid sensing mechanism of H. pylori, the two-component system (TCS) ArsRS. ArsRS induces hsdM1 expression under acidic conditions. The acid response of hsdM1 is unique among the Type I DNA methyltransferases (MTases) and the two Type II MTases in H. pylori 26695 selected for the current study. In addition, transcription of hsdM1 and hsdM2 (HP0850), another Type I MTase, appear to be under the regulation of the protein LuxS. While there is debate surrounding the role of LuxS in H. pylori, we propose that LuxS is acting in a quorum-sensing role within this system. The selected Type II MTases, M.HpyAI (HP1208) and M.HpyAII (HP1368), do not follow the observed patterns or exhibit any significant changes in gene expression upon acid exposure or resuspension in new media. This indicates that our findings are hsdM1 and Type I methyltransferase-specific. We also conducted a prolonged acid exposure experiment with the H. pylori 26695 control mutant, ΔarsS mutant, ΔhsdM1 mutant, and hsdM1-repair mutant to determine the impacts of differential acid conditions and MTase expression on the methylome. The DNA methyltransferase hsdM1 in H. pylori strain 26695 is acid and quorum-sensitive, and thus may contribute to methylome plasticity to aid the bacterium in colonizing the harsh and volatile environment of the human gastric epithelium.
Zimmerman, Elise, "The Characterization of the Type I DNA Methyltransferase hsdM1 (HP0463) in Helicobacter pylori" (2022). Undergraduate Honors Theses. William & Mary. Paper 1782.
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