Purine salvage in Helicobacter pylori
Miller, Erica Francesca
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Purines are essential for all living cells. This fact is reflected in the high degree of pathway conservation for purine metabolism across all domains of life. The availability of purines within a mammalian host is thought to be a limiting factor for infection, as demonstrated by the importance of purine synthesis and salvage genes among many bacterial pathogens. Helicobacter pylori, a primary causative agent of peptic ulcers and gastric cancers, colonizes a niche that is otherwise uninhabited by bacteria: the surface of the human gastric epithelium. Despite many studies over the past 30 years that have addressed virulence mechanisms such as acid resistance, little knowledge exists regarding this organism’s purine metabolism. To fill this gap in knowledge, we asked whether H. pylori can carry out de novo purine biosynthesis, and whether its purine salvage network is complete. Based on genomic data from the fully sequenced H. pylori genomes, we combined mutant analysis with physiological studies to determine that H. pylori, by necessity, must acquire purines from its human host. Furthermore, we found the purine salvage network to be complete, allowing this organism to use any single purine nucleobase or nucleoside for growth. In the process of elucidating these pathways, we discovered a nucleoside transporter in H. pylori that, in contrast to the biochemically-characterized homolog NupC, aids in uptake of purine rather than pyrimidine nucleosides into the cell. Lastly, we investigated an apparent pathway gap in the genome annotation—that of adenine degradation—and in doing so uncovered a new family of adenosine deaminase that lacks sequence homology with all other adenosine deaminases studied to date. These newly characterized H. pylori proteins exemplify evolution in action, and underscore the need for functional annotations that do not rely solely on sequence homology with biochemically characterized orthologs. The results of our studies expand the database that is needed for future genome annotations and for prediction of metabolic capabilities in other prokaryotes.