title: Helicobacter pylori relies primarily on the purine salvage pathway for purine nucleotide biosynthesis.
abstract: Helicobacter pylori is a chronic colonizer of the gastric epithelium and plays a major role in the development of gastritis, peptic ulcer disease, and gastric cancer. In its coevolution with humans, the streamlining of the H. pylori genome has resulted in a significant reduction in metabolic pathways, one being purine nucleotide biosynthesis. Bioinformatic analysis has revealed that H. pylori lacks the enzymatic machinery for de novo production of IMP, the first purine nucleotide formed during GTP and ATP biosynthesis. This suggests that H. pylori must rely heavily on salvage of purines from the environment. In this study, we deleted several genes putatively involved in purine salvage and processing. The growth and survival of these mutants were analyzed in both nutrient-rich and minimal media, and the results confirmed the presence of a robust purine salvage pathway in H. pylori. Of the two phosphoribosyltransferase genes found in the H. pylori genome, only gpt appears to be essential, and an Δapt mutant strain was still capable of growth on adenine, suggesting that adenine processing via Apt is not essential. Deletion of the putative nucleoside phosphorylase gene deoD resulted in an inability of H. pylori to grow on purine nucleosides or the purine base adenine. Our results suggest a purine requirement for growth of H. pylori in standard media, indicating that H. pylori possesses the ability to utilize purines and nucleosides from the environment in the absence of a de novo purine nucleotide biosynthesis pathway.
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia Health System, Charlottesville, Virginia, USA.
authors.forename: George
authors.initials: G
authors.lastname: Liechti
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Goldberg
mesh_terms: D000228:Adenine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D016480:Helicobacter pylori / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D010430:Pentosyltransferases / Q000235:genetics / Q000378:metabolism; D011684:Purine Nucleosides / Q000378:metabolism; D011685:Purine Nucleotides / Q000096:biosynthesis* / Q000378:metabolism; D011687:Purines / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D011684:Purine Nucleosides; D011685:Purine Nucleotides; D011687:Purines; D010430:Pentosyltransferases; C067995:nucleoside phosphorylase; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase