Abstract
The ability to synthesize and salvage purines is crucial for colonization by a variety of human bacterial pathogens. Helicobacter pylori colonizes the gastric epithelium of humans, yet its specific purine requirements are poorly understood, and the transport mechanisms underlying purine uptake remain unknown. Using a fully defined synthetic growth medium, we determined that H. pylori 26695 possesses a complete salvage pathway that allows for growth on any biological purine nucleobase or nucleoside with the exception of xanthosine. Doubling times in this medium varied between 7 and 14 hours depending on the purine source, with hypoxanthine, inosine and adenosine representing the purines utilized most efficiently for growth. The ability to grow on adenine or adenosine was studied using enzyme assays, revealing deamination of adenosine but not adenine by H. pylori 26695 cell lysates. Using mutant analysis we show that a strain lacking the gene encoding a NupC homolog (HP1180) was growth-retarded in a defined medium supplemented with certain purines. This strain was attenuated for uptake of radiolabeled adenosine, guanosine, and inosine, showing a role for this transporter in uptake of purine nucleosides. Deletion of the GMP biosynthesis gene guaA had no discernible effect on mouse stomach colonization, in contrast to findings in numerous bacterial pathogens. In this study we define a more comprehensive model for purine acquisition and salvage in H. pylori that includes purine uptake by a NupC homolog and catabolism of adenosine via adenosine deaminase.
Highlights
The bacterial pathogen Helicobacter pylori is known for its ability to colonize and persist in the human stomach, a niche that is largely uninhabited by other bacteria
Similar to other pathogens that have evolved in close association with their hosts [23,24,25], H. pylori does not have the ability to synthesize purines de novo [5], a conclusion that our study confirmed for H. pylori 26695 using a fully defined medium that obviates the need for biological supplements typically added at high concentrations (5% bovine serum albumin (BSA) and/or 10% foetal bovine serum (FBS), for example)
We showed all individual biological purines except xanthosine allow for growth, but certain nucleosides and nucleobases support faster growth
Summary
The bacterial pathogen Helicobacter pylori is known for its ability to colonize and persist in the human stomach, a niche that is largely uninhabited by other bacteria. Infection by H. pylori greatly increases the risk of duodenal and gastric ulcers, gastric cancers, and MALT lymphoma [1]. As it infects between 20%–80% of the adult population worldwide, H. pylori is regarded as one of the most successful human pathogens [1]. J., Annual Meeting of the American Society for Microbiology, May 2011), a result confirmed for three other strains of H. pylori [5]. These observations corroborate predictions made from the RASTannotated H. pylori genomes, which all lack the pathway for de novo IMP synthesis [6]. Several different strains were used for these prior studies, the gene homologs for purine salvage are well-conserved among the sequenced strains of H. pylori, making it likely that purine utilization is similar across strains [6]
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