Background em Helicobacter pylori /em ( em Hp /em ), a human being pathogen that is associated with gastritis, peptic ulcer, and gastric malignancy, has been regarded as a microaerophile, but there is no general consensus about its specific O2 requirements. under the aerobic condition. CO2 deprivation for less than 24 h did not markedly switch cytoplasmic or periplasmic pH, suggesting that cellular pH homeostasis only cannot account for the capnophilic nature of em Hp /em . Further, CO2 deprivation significantly increased intracellular levels of ppGpp and ATP but significantly decreased cellular mRNA levels, suggesting induction of the stringent Rabbit Polyclonal to SFRS17A response. Conclusions We conclude, unlike previous reports, that em H. pylori /em may be a capnophilic aerobe whose growth is promoted by atmospheric oxygen levels in the presence of 10% CO2. Our data also suggest that buffering of intracellular pH alone cannot account for the CO2 requirement of em H. pylori /em and that CO2 deprivation initiates the stringent response in em H. pylori /em . Our findings may provide new insight into the physiology of this fastidious human pathogen. strong class=”kwd-title” Keywords: Helicobacter pylori, growth, atmospheric oxygen level, carbon dioxide Background Oxygen is usually important for many organisms; because of its high redox potential, it is a common electron acceptor in cellular respiration. However, diverse metabolic reactions generate cell-damaging reactive oxygen species such as superoxide (O2-) and hydrogen peroxide as byproducts. In response, cells have developed oxidative stress defense systems to protect themselves from oxidative damage. Microorganisms are classified into three large categories–aerobic, anaerobic, and microaerophilic–on the basis of their ability Enzastaurin distributor to use oxygen as an electron acceptor during ATP generation. Microaerophiles show optimal growth at 2% to 10% O2, but cannot survive under the normal atmospheric level of O2 . em Helicobacter pylori /em ( em Hp /em ) is usually a gram-negative human pathogen that resides in the mucus layer of the stomach. It affects more than half of the world’s populace and is often associated with gastritis, peptic ulcer, and gastric cancer [2,3]. Numerous studies have shown that em Hp /em uses both aerobic respiration and fermentation pathways. Complete genome sequencing and studies of em Hp /em metabolism and physiology indicate that em Hp /em uses glucose as its primary energy and carbon source by the Entner-Doudoroff and pentose phosphate pathways [4-9]. Depending on culture conditions, em Hp /em anaerobically produces lactate and acetate from pyruvate or aerobically produces acetate or CO2 [4,7,10,11]. em Hp /em metabolizes pyruvate by the anaerobic mixed acid fermentation pathway, accumulating alanine, lactate, acetate, formate, and succinate . It also uses the tricarboxylic acid cycle, which appears to be a noncyclic, branched pathway characteristic of anaerobic metabolism that produces succinate in the reductive dicarboxylic acid branch and -ketoglutarate in the oxidative tricarboxylic acid branch . em Hp /em constitutively expresses the aerobic respiratory chain with a em cbb /em 3-type cytochrome c oxidase as the terminal oxidase . Whole genome analysis of two em Hp /em strains revealed the presence of genes encoding components of the membrane-embedded F0 proton channel and the catalytic F1 complex, suggesting that em Hp /em produces a significant portion of its ATP by aerobic respiration [9,15]. In addition, em Hp /em uses anaerobic respiration utilizing H2 as an electron donor . Since its discovery in 1984, em Hp /em has been considered a microaerophilic bacterium highly susceptible to environmental O2 tension . em Hp /em is usually a spiral-shaped bacillus that, when exposed to a high O2 concentration, converts to a full coccoid form that is viable but nonculturable [18,19]. em Hp /em is generally cultured under microaerobic conditions using a GasPak or CO2 chamber to achieve adequate growth, and its cultivation can be difficult and cumbersome . Therefore, significant efforts have been made to increase the efficiency of em Hp /em cultivation [21-23]. There are Enzastaurin distributor numerous hypotheses for the microaerophilic requirements of bacteria: high sensitivity to toxic forms of oxygen present in the culture medium, excessive metabolic generation of toxic forms of oxygen, low respiratory rates, iron deficiency, lack of protective enzymes, unusually oxygen-sensitive cell constituents, and reliance on oxygen-labile substrates (see reference  for review). The antioxidant defense system of em Hp /em has been studied extensively because of its unique microaerophilic nature and clinical importance. em Hp /em has been found to express oxidative stress resistance enzymes including superoxide dismutase Enzastaurin distributor (SodB), catalase (KatA), as well as peroxiredoxins, alkyl hydroxide reductases, bacterioferritin co-migratory protein and thiol peroxidase (see reference  for review). In addition, em Hp /em expresses neutrophil-activating protein (NapA), which protects cells from oxidative stress damage, DNA repair proteins (Nth, MutS, RuvC), an oxidized protein repair system (Msr), and the thioredoxin system (thioredoxin and thioredoxin reductase) . Despite these diverse antioxidant systems, em Hp Enzastaurin distributor /em remains vulnerable to the toxicity of environmental levels of oxygen. Several lines of evidence have suggested that em Hp /em may not be microaerophilic. em Hp /em strains exhibit a range of susceptibility to high.