Purine metabolism and the microaerophily of Helicobacter pylori.
The requirements for purine nucleotide synthesis, the effects of purine analogues, and the metabolism of adenine in the bacterium Helicobacter pylori were investigated employing cell culture techniques and one-dimensional NMR spectroscopy. Bacterial cells grew and proliferated in media lacking preformed purines, indicating that H. pylori can synthesize purine nucleotides de novo to meet its requirements. Blocking of this pathway in the absence of sufficient preformed purines for salvage nucleotide synthesis led to cell death. Analogues of purine nucleobases and nucleosides taken up by the cells were cytotoxic, suggesting that salvage routes could be exploited for therapy. Adenine or hypoxanthine were able to substitute for catalase in supporting cell growth and proliferation, suggesting a role for these bases in maintaining the microaerophilic conditions essentially required by the bacterium.
Mendz
G L
GL
School of Biochemistry and Molecular Genetics, School of Microbiology and Immunology, The University of New South Wales, Sydney, Australia. g.mendz@unsw.edu.au
Shepley
A J
AJ
Hazell
S L
SL
Smith
M A
MA
D000225:Adenine / Q000494:pharmacology; D000619:Aminohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003470:Culture Media / Q000378:metabolism / Q000494:pharmacology; D004357:Drug Synergism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D016480:Helicobacter pylori / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019271:Hypoxanthine / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D011685:Purine Nucleotides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011687:Purines / Q000037:antagonists & inhibitors / Q000378:metabolism
D003470:Culture Media; D016166:Free Radical Scavengers; D006131:Growth Inhibitors; D011685:Purine Nucleotides; D011687:Purines; D019271:Hypoxanthine; D000620:Aminoimidazole Carboxamide; D006861:Hydrogen Peroxide; D002374:Catalase; D000619:Aminohydrolases; C018774:adenine deaminase; D000225:Adenine; D010100:Oxygen