acid-phosphatase and Helicobacter-Infections

Topics: Acetylglucosaminidase; Acid Phosphatase; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Autophagosomes; Autophagy; Autophagy-Related Protein 5; Calcium; Carrier Proteins; Cathelicidins; Cell Line; Cholecalciferol; Epithelial Cells; Helicobacter Infections; Helicobacter pylori; Humans; Lysosomes; Male; Mice, Inbred C57BL; Protein Disulfide-Isomerases; Receptors, Calcitriol; STAT3 Transcription Factor; Stomach; Transient Receptor Potential Channels

Twenty-six Helicobacter pylori targeted mutant strains with deficiencies in oxidative stress combating proteins, including 12 double mutant strains were analyzed via physiological and proteomic approaches to distinguish the major expression changes caused by the mutations. Mutations were introduced into both a Mtz(S) and a Mtz(R) strain background. Most of the mutations caused increased growth sensitivity of the strains to oxygen, and they all exhibited clear compensatory up-expression of oxidative stress resistance proteins enabling survival of the bacterium. The most frequent up-expressed oxidative stress resistance factor (observed in 16 of the mutants) was the iron-sequestering protein NapA, linking iron sequestration with oxidative stress resistance. The up-expression of individual proteins in mutants ranged from 2 to 10 fold that of the wild type strain, even when incubated in a low O(2) environment. For example, a considerably higher level of catalase expression (4 fold of that in the wild-type strain) was observed in ahpC napA and ahpC sodB double mutants. A Fur mutant up-expressed ferritin (Pfr) protein 20-fold. In some mutant strains the bacterial DNA is protected from oxidative stress damage apparently via overexpression of oxidative stress-combating proteins such as NapA, catalase or MdaB (an NADPH quinone reductase). Our results show that H. pylori has a variety of ways to compensate for loss of major oxidative stress combating factors.

Topics: Acid Phosphatase; Animals; Bacterial Proteins; Catalase; DNA; DNA Damage; DNA Fragmentation; Drug Resistance, Neoplasm; Electrophoresis, Agar Gel; Electrophoresis, Polyacrylamide Gel; Escherichia coli; Escherichia coli Proteins; Ferritins; Heat-Shock Proteins; Helicobacter Infections; Helicobacter pylori; Hydroxyl Radical; Iron; Metronidazole; Mice; Mutation; Oxidative Stress; Oxygen; Phenotype; Plasmids; Proteomics; R Factors; Repressor Proteins; Time Factors; Up-Regulation