The precise mechanism for the growth inhibition by high O2 levels is under investigation. Numerous studies have been carried out to elucidate Hp physiology under oxidative stress, including studies of selleck chemicals morphology, gene expression, and protein expression. However, in some of these experiments, Hp was cultured under atmospheric O2 tension without supplemental CO2 [29, 49–51]. Therefore, coccoid transformation and subsequent cellular changes may have resulted, at least in part, from CO2 deprivation rather than oxidative stress. A unique feature of Hp is its transformation to coccoid form under stress conditions.
Coccoid transformation was thought to be a passive conversion that eventually leads to cell death . However, several recent reports have suggested that coccoid transformation is an active process that allows Hp to adapt to its environment [52–54]. In the
present study, CO2 deprivation induced coccoid formation, but this morphological transformation was delayed in cells cultured under high O2 tension, supporting the view that coccoid transformation of Hp is not a passive process but an active energy-consuming process. In this study, we observed that actively growing cells, but not those at a stationary phase, produce OMVs, which are discrete, closed outer membrane blebs produced by gram-negative bacteria, especially pathogenic strains . They are believed to serve as secretory vesicles that transmit virulence factors to host cells. OMVs are released by actively growing Combretastatin A4 cells, and their maximal production occurs at the end of log phase in E. coli, Vibrio cholerae, and Brucella melitensis [56–58]. Hp OMVs are involved in biofilm formation in vitro and deliver VacA cytotoxin to gastric epithelium [59, 60]. They induce growth arrest and IL-8 production by gastric epithelial cells, which have been associated Methisazone with gastritis caused by Hp infections [61, 62], and also enhances the carcinogenic potential of Hp . Taken together, these reports and results obtained in the present study indicate the higher virulence of actively growing Hp cells, which are able to damage host cells
through toxin delivery. In the present study, 17-AAG mouse cultivation of Hp cells in the absence of CO2 increased intracellular ppGpp levels, suggesting induction of the stringent response, which induces a global alteration in cellular transcription and indirectly activates genes involved in amino acid biosynthesis [42, 64]. Many factors induce the stringent response, but nutrient stress from amino acid starvation has been the best studied. Induction of the stringent response by CO2 deprivation has also been reported in Campylobacter jejuni, a capnophilic microaerophile that is closely related to Hp . The bicarbonate concentration of gastric juice is approximately 25 mM . Hp generates additional CO2 via the breakdown of urea, thereby increasing bicarbonate levels.