Stimulation of growth of the human gastric pathogen Helicobacter pylori by atmospheric level of oxygen under high carbon dioxide tension

BACKGROUND: Helicobacter pylori (Hp), a human pathogen that is associated with gastritis, peptic ulcer, and gastric cancer, has been considered a microaerophile, but there is no general consensus about its specific O(2 )requirements. A clear understanding of Hp physiology is needed to elucidate the pathogenic mechanism(s) of Hp infection. RESULTS: We cultured Hp under a range of O(2 )levels with or without 10% CO(2 )and evaluated growth profiles, morphology, intracellular pH, and energy metabolism. We found that, in the presence of 10% CO(2), the normal atmospheric level of O(2 )inhibited Hp growth at low density but stimulated growth at a higher density. Field emission scanning electron microscopy and fluorescence microscopy of Hp cells cultured under 20% O(2 )tension revealed live spiral-shaped bacteria with outer membrane vesicles on a rugged cell surface, which became smooth during the stationary phase. Fermentation products including acetate, lactate, and succinate were detected in cell culture media grown under microaerobic conditions, but not under the aerobic condition. CO(2 )deprivation for less than 24 h did not markedly change cytoplasmic or periplasmic pH, suggesting that cellular pH homeostasis alone cannot account for the capnophilic nature of Hp. Further, CO(2 )deprivation significantly increased intracellular levels of ppGpp and ATP but significantly decreased cellular mRNA levels, suggesting induction of the stringent response. CONCLUSIONS: We conclude, unlike previous reports, that H. pylori may be a capnophilic aerobe whose growth is promoted by atmospheric oxygen levels in the presence of 10% CO(2). Our data also suggest that buffering of intracellular pH alone cannot account for the CO(2 )requirement of H. pylori and that CO(2 )deprivation initiates the stringent response in H. pylori. Our findings may provide new insight into the physiology of this fastidious human pathogen.